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Tollabi M, Poursalehi Z, Mehrafshar P, Bakhtiari R, Sarmadi VH, Tayebi L, Haramshahi SMA. Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration. Connect Tissue Res 2024; 65:343-363. [PMID: 39297793 PMCID: PMC11541888 DOI: 10.1080/03008207.2024.2396002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/06/2024] [Accepted: 08/19/2024] [Indexed: 10/17/2024]
Abstract
Features of the extracellular matrix, along with biochemical factors, have a momentous impress in making genes on and/or off. The interaction of cells and the extracellular matrix is mediated by integrins. Therefore, these molecules have pivotal roles in regulating cell behaviors. Integrins include a group of molecules with a variety of characteristics that can affect different molecular cascades. Considering the importance of these molecules in tissue regeneration after injury, it is necessary to know well the integrins involved in the process of connecting cells to the extracellular matrix in each tissue.With the increase in life expectancy, bone tissue engineering has received more attention from researchers. Integrins are critical components in osteoblast differentiation, survival, and bone mechanotransduction. During osteogenic differentiation in stem cells, specific integrins facilitate multiple signaling pathways through their cytoplasmic domain, leading to the induction of osteogenic differentiation. Also, due to the importance of using biomaterials in bone tissue engineering, efforts have been made to design and use biomaterials with maximum interaction with integrins. Notably, the use of RGD peptide or fibronectin for surface modification is a well-established and commonly employed approach to manipulate integrin activity.This review article looks into integrins' role in bone development and regeneration. It then goes on to explore the complex mechanisms by which integrins contribute to these processes. In addition, this review discusses the use of natural and synthetic biomaterials that target integrins to promote bone regeneration.
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Affiliation(s)
- Mohammad Tollabi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Poursalehi
- Department of Applied Cell Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Parichehr Mehrafshar
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Vahid Hosseinpour Sarmadi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Lobat Tayebi
- Marquette University School of Dentistry, Milwaukee, WI, 53233, USA
| | - Seyed Mohammad Amin Haramshahi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Hazrate Fatemeh Hospital, Iran University of Medical Sciences, Tehran, Iran
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Dong M, Wang W, Wu W, Cheng X, Cheng J, Wang L, Song L. A novel surface marker CD49d promotes TNF expression in oyster agranulocytes by mediating the MAPK pathway. FISH & SHELLFISH IMMUNOLOGY 2024; 151:109702. [PMID: 38897309 DOI: 10.1016/j.fsi.2024.109702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 06/09/2024] [Accepted: 06/13/2024] [Indexed: 06/21/2024]
Abstract
CD49d, encoded by the gene Integrin α4, is a significant member of cell adhesion receptors, which is widely expressed in various immune cells to trigger immune responses against invading pathogens. In the present study, the expression of CgCD49d and its regulatory role in TNF expression were investigated in the Pacific oyster Crassostrea gigas. There were five Int-alpha domains, an Integrin_alpha2 region and a unique FG-GAP repeat region inserted identified in CgCD49d. CgCD49d transcript was specifically expressed in haemocytes, and its mRNA expression level in haemocytes increased after LPS and Vibrio splendidus stimulation. After CgCD49d was blocked by using its antibody, the phosphorylation level of CgJNK in the MAPK signaling pathway and CgTNF transcripts decreased significantly post V. splendidus stimulation. After phosphorylation level of CgJNK was inhibited by using its inhibitor, the nuclear translocation of CgRel was restrained and CgTNF transcripts also decreased significantly post V. splendidus stimulation. Furthermore, CgCD49d was found to be mainly expressed in the agranulocyte subpopulation, and Alexa Fluor 488-conjugated CgCD49d antibody labeled agranulocytes with a circle of green fluorescence signals on CgCD49d+ agranulocyte surface under Confocal microscopy, which accounted for 24.9 ± 4.53% of total haemocytes. Collectively, these results suggested that CgCD49d promoted TNF expression in oyster haemocytes against bacterial invasion by mediating MAPK pathway, and it could be used as a surface marker to type and sort a subset of agranulocyte subpopulation among haemocytes.
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Affiliation(s)
- Miren Dong
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China
| | - Weilin Wang
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Dalian Key Laboratory of Aquatic Animal Disease Prevention and Control, Dalian Ocean University, Dalian, 116023, China.
| | - Wei Wu
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China
| | - Xuemei Cheng
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China
| | - Junlei Cheng
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China
| | - Lingling Wang
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Dalian Key Laboratory of Aquatic Animal Disease Prevention and Control, Dalian Ocean University, Dalian, 116023, China
| | - Linsheng Song
- Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Dalian Key Laboratory of Aquatic Animal Disease Prevention and Control, Dalian Ocean University, Dalian, 116023, China.
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Johnson GA, Burghardt RC, Bazer FW, Seo H, Cain JW. Integrins and their potential roles in mammalian pregnancy. J Anim Sci Biotechnol 2023; 14:115. [PMID: 37679778 PMCID: PMC10486019 DOI: 10.1186/s40104-023-00918-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/10/2023] [Indexed: 09/09/2023] Open
Abstract
Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix (ECM) interactions leading to assembly of integrin adhesion complexes (IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus (embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium (LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.
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Affiliation(s)
- Gregory A Johnson
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4459, USA.
| | - Robert C Burghardt
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4459, USA
| | - Fuller W Bazer
- Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX, 77843-2471, USA
| | - Heewon Seo
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4459, USA
| | - Joe W Cain
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4459, USA
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Chen Y, Chen Y, Jian B, Feng Q, Liu L. Identification and Expression of Integrins during Testicular Fusion in Spodoptera litura. Genes (Basel) 2023; 14:1452. [PMID: 37510356 PMCID: PMC10379305 DOI: 10.3390/genes14071452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/10/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Integrin members are cell adhesion receptors that bind to extracellular matrix (ECM) proteins to regulate cell-cell adhesion and cell-ECM adhesion. This process is essential for tissue development and organogenesis. The fusion of two testes is a physiological phenomenon that is required for sperm production and effective reproduction in many Lepidoptera. However, the molecular mechanism of testicular fusion is unclear. In Spodoptera litura, two separated testes fuse into a single testis during the larva-to-pupa transformation. We identified five α and five β integrin subunits that were closely associated with testicular fusion. Integrin α1 and α2 belong to the position-specific 1 (PS1) and PS2 groups, respectively. Integrin α3, αPS1/αPS2, and αPS3 were clustered into the PS3 group. Integrin β1 belonged to the insect β group, and β2, β3, and β5 were clustered in the βν group. Among these integrins, α1, α2, α3, αPS1/PS2, αPS3, β1, and β4 subunits were highly expressed when the testes fused. However, their expression levels were much lower before and after the fusion of the testis. The qRT-PCR and immunohistochemistry analyses indicated that integrin β1 mRNA and the protein were highly expressed in the peritoneal sheath of the testis, particularly when the testes fused. These results indicate that integrins might participate in S. litura testicular fusion.
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Affiliation(s)
- Yaqing Chen
- Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
- Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Yu Chen
- Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
- Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Baozhu Jian
- Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
- Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Qili Feng
- Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
- Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Lin Liu
- Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
- Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
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A review on regulation of cell cycle by extracellular matrix. Int J Biol Macromol 2023; 232:123426. [PMID: 36708893 DOI: 10.1016/j.ijbiomac.2023.123426] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/12/2023] [Accepted: 01/21/2023] [Indexed: 01/26/2023]
Abstract
The extracellular matrix (ECM) is a network of structural proteins, glycoproteins and proteoglycans that assists independent cells in aggregating and forming highly organized functional structures. ECM serves numerous purposes and is an essential component of tissue structure and functions. Initially, the role of ECM was considered to be confined to passive functions like providing mechanical strength and structural identity to tissues, serving as barriers and platforms for cells. The doors to understanding ECM's proper role in tissue functioning opened with the discovery of cellular receptors, integrins to which ECM components binds and influences cellular activities. Understanding and utilizing ECM's potential to control cellular function has become a topic of much interest in recent decades, providing different outlooks to study processes involved in developmental programs, wound healing and tumour progression. On another front, the regulatory mechanisms operating to prevent errors in the cell cycle have been topics of a titanic amount of studies. This is expected as many diseases, most infamously cancer, are associated with defects in their functioning. This review focuses on how ECM, through different methods, influences the progression of the somatic cell cycle and provides deeper insights into molecular mechanisms of functional communication between adhesion complex, signalling pathways and cell cycle machinery.
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Immune Monitoring of Paediatric Patients Infected with Rickettsia rickettsii, Ehrlichia canis and Coinfected. Pathogens 2022; 11:pathogens11111351. [PMID: 36422602 PMCID: PMC9696171 DOI: 10.3390/pathogens11111351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 11/07/2022] [Accepted: 11/08/2022] [Indexed: 11/17/2022] Open
Abstract
In 2021, 273 Rocky Mountain spotted fever cases were reported nationwide in Mexico. In Chihuahua City, fourteen samples were obtained from children suspected of rickettsial infection. The analysis of samples (January to December 2021) showed prevalence rates of 28.5%, 43%, and 28.5% for Rickettsia rickettsii, Ehrlichia canis, and both pathogens in coinfection, respectively. The analysis of clinical haematological and biochemistry analytes showed alterations; 100% of the children had elevated liver enzymes and coagulation times, 64% showed leukocytosis due to neutrophilia, 55% had thrombocytopenia, lymphopenia, and hypoalbuminemia, and 45% showed normocytic normochromic anaemia. Statistically significant differences were observed in the expression of the chemokines IL-8, RANTES, CXCL9/MIG, and CXCL10/IP-10 across the coinfected and control groups, and the difference in IP-10 expression was significant for patients infected by R. rickettsii compared to the control group. Additionally, significant differences were observed for expression levels of IL-1β, IL-6, IL-17, IFNγ, and TNFα among the R. rickettsii-positive group compared to the control group. On the other hand, the coinfected group exhibited modified levels of IL-6, IL-8, and IL-10 compared with the control group. Finally, significant differences were observed for CD8+ T lymphocyte subpopulations between individuals positive for R. rickettsii and those positive for E. canis.
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Xiong X, Yang H, Ding C, Qin B, Deng Y, Xiong L, Liu X, Li Y, Xiao T, Lv Z. Functional and expression analysis reveals the involvement of integrin αvβ3 in antiviral immunity of grass carp (Ctenopharyngodon idella). FISH & SHELLFISH IMMUNOLOGY 2022; 129:52-63. [PMID: 35995370 DOI: 10.1016/j.fsi.2022.08.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 08/01/2022] [Accepted: 08/15/2022] [Indexed: 06/15/2023]
Abstract
Integrins are α-β heterodimeric cell receptors that can bind the protein components of pathogens, and play crucial roles in mammalian immune responses, but the immune functions mediated by integrins remains largely unknown in teleost fish. In this study, an integrin αvβ3 (GCαvβ3) originally assembled by αv (GCαv) and β3 (GCβ3) subunits, was identified from a teleost fish grass carp Ctenopharyngodon idella. The pairwise alignment analyses showed that the amino acid sequences of GCαv and GCβ3 shared high similarity (75.2-95.1%) and identity (58.6-90.7%) with their homologs from other vertebrates. Both GCαv and GCβ3 harbored the conserved protein domains and motifs, and were clustered in fish branch of the phylogenetic tree containing the counterparts from various vertebrates. Co-immunoprecipitation displayed that GCβ3 could interact with the grass carp reovirus (GCRV) outer capsid protein VP5. Two incubation experiments revealed that the interaction of GCRV or VP5 proteins with GCβ3 could induce the expressions of type I interferons (IFNs) including IFN2 and IFN3 in grass carp ovary cell line. The functional analysis demonstrated that GCαvβ3 served as a receptor of viral protein components to be involved in antiviral immunity as human integrin αvβ3 did. In addition, both GCαv and GCβ3 were significantly upregulated in various tissues of grass carp after GCRV infection. This study might provide fundamental basis for understanding the molecular characteristics and immune functions of GCαvβ3, and offer a new insight into the antiviral immune mechanism specific to the integrins in grass carp.
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Affiliation(s)
- Xiaoqing Xiong
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Hong Yang
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Chunhua Ding
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Beibei Qin
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Yadong Deng
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Liming Xiong
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Xiaoyan Liu
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China
| | - Yaoguo Li
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China
| | - Tiaoyi Xiao
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China.
| | - Zhao Lv
- Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, 410128, China.
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Chen J, St Johnston D. Epithelial Cell Polarity During Drosophila Midgut Development. Front Cell Dev Biol 2022; 10:886773. [PMID: 35846367 PMCID: PMC9281564 DOI: 10.3389/fcell.2022.886773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/30/2022] [Indexed: 11/23/2022] Open
Abstract
The adult Drosophila midgut epithelium is derived from a group of stem cells called adult midgut precursors (AMPs) that are specified during the migration of the endoderm in early embryogenesis. AMPs are maintained and expanded in AMP nests that lie on the basal side of the larval midgut throughout the larval development. During metamorphosis, the larval midgut undergoes histolysis and programmed cell death, while the central cells in the AMP nests form the future adult midgut and the peripheral cells form the transient pupal midgut. Here we review what is known about how cells polarise in the embryonic, larval, pupal and adult midgut, and discuss the open questions about the mechanisms that control the changes in cell arrangements, cell shape and cell polarity during midgut development.
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Affiliation(s)
| | - Daniel St Johnston
- Gurdon Institute and the Department of Genetics, University of Cambridge, Cambridge, United Kingdom
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Kausar S, Abbas MN, Gul I, Liu Y, Tang BP, Maqsood I, Liu QN, Dai LS. Integrins in the Immunity of Insects: A Review. Front Immunol 2022; 13:906294. [PMID: 35757717 PMCID: PMC9218073 DOI: 10.3389/fimmu.2022.906294] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/02/2022] [Indexed: 12/30/2022] Open
Abstract
Integrins are a large group of cell-surface proteins that are classified as transmembrane proteins. Integrins are classified into different types based on sequence variations, leading to structural and functional diversity. They are broadly distributed in animals and have a wide range of biological functions such as cell-to-cell communication, intracellular cytoskeleton organization, cellular signaling, immune responses, etc. Integrins are among the most abundant cell surface proteins in insects, exhibiting their indispensability in insect physiology. Because of their critical biological involvement in physiological processes, they appear to be a novel target for designing effective pest control strategies. In the current literature review, we first discuss the discovery and expression responses of integrins against various types of pathogens. Secondly, we examine the specific biological roles of integrins in controlling microbial pathogens, such as phagocytosis, encapsulation, nodulation, immune signaling, and so on. Finally, we describe the possible uses of integrins to control agricultural insect pests.
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Affiliation(s)
- Saima Kausar
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China
| | - Muhammad Nadeem Abbas
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China
| | - Isma Gul
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China
| | - Yu Liu
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Bo-Ping Tang
- Jiangsu Key Laboratory for Bioresources of Saline Soils, Jiangsu Synthetic Innovation Center for Coastal Bio-agriculture, Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, School of Wetlands, Yancheng Teachers University, Yancheng, China
| | - Iram Maqsood
- Department of Zoology, Shaheed Benazir Bhutto Woman University, Peshawar, Pakistan
| | - Qiu-Ning Liu
- Jiangsu Key Laboratory for Bioresources of Saline Soils, Jiangsu Synthetic Innovation Center for Coastal Bio-agriculture, Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, School of Wetlands, Yancheng Teachers University, Yancheng, China.,Key Laboratory of Insect Developmental and Evolutionary Biology, Chinese Academy of Sciences (CAS) Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China
| | - Li-Shang Dai
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
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Denizot AL, L'Hostis A, Sallem A, Favier S, Pierre R, Do Cruzeiro M, Guilbert T, Burlet P, Lapierre JM, Robain M, Le Lorc'H M, Vicaut E, Chatzovoulou K, Steffann J, Romana S, Méhats C, Santulli P, Patrat C, Vaiman D, Ziyyat A, Wolf JP. Cyclic fertilin-derived peptide stimulates in vitro human embryo development. F&S SCIENCE 2022; 3:49-63. [PMID: 35559995 DOI: 10.1016/j.xfss.2021.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 12/11/2021] [Accepted: 12/16/2021] [Indexed: 06/15/2023]
Abstract
OBJECTIVE To study the cyclic fertilin peptide effects on preimplantation human embryogenesis. Cyclic fertilin peptide reproduces the structure of the binding site of the sperm Fertilin β (also named A Disintegrin and Metalloprotease 2: ADAM2) disintegrin domain. It binds to the oocyte membrane and increases sperm-oocyte fusion index in human and fertilization rate in mouse, providing healthy pups. It also improves human oocyte maturation and chromosome segregation in meiosis I and binds to human embryo blastomeres, suggesting that it has a membrane receptor. DESIGN Thawed human embryos at the 3 to 4 cells stage were randomly included in a dose-response study with cyclic fertilin peptide. Inner cell mass (ICM), trophectoderm (TE), and total cell numbers were evaluated in top- and good-quality blastocysts. SETTING The study was performed in an academic hospital and research laboratory. PATIENT(S) Human embryos donated for research. This project was approved by the French "Agence de la Biomédecine." INTERVENTION(S) Immunofluorescence and tissue-specific gene expression analysis, using Clariom D microarrays, were performed to study its mechanism of action. MAIN OUTCOME MEASURE(S) Cyclic fertilin peptide improves blastocyst formation by almost 20%, the concentration of 1 μM being the lowest most efficient concentration. It significantly increases twice the TE cell number, without modifying the ICM. It increases the in vitro hatching rate from 14% to 45%. RESULT(S) Cyclic fertilin peptide stimulates TE growth. In the ICM, it induces transcriptional activation of intracellular protein and vesicle-mediated transport. CONCLUSION(S) Cyclic fertilin peptide dramatically improves human embryo development potential. It could be used to supplement culture medium and improve the in vitro human embryo development. Starting supplementation immediately after fertilization, instead of day 2, could significantly upgrade assisted reproductive technology outcome.
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Affiliation(s)
- Anne-Lyse Denizot
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France; Department "Histologie-Embryologie-Biologie de la Reproduction," Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Audrey L'Hostis
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France; Department "Histologie-Embryologie-Biologie de la Reproduction," Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Amira Sallem
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France; Department "Histologie-Embryologie-Biologie de la Reproduction," Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Laboratoire d'Histologie-Embryologie et Cytogénétique (LR 18 ES 40), Faculté de Médecine de Monastir, Tunisie
| | - Sophie Favier
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France
| | - Rémi Pierre
- Homologous Recombination, Embryo Transfer and Cryopreservation Facility, Cochin Institute, University of Paris, Paris, France
| | - Marcio Do Cruzeiro
- Homologous Recombination, Embryo Transfer and Cryopreservation Facility, Cochin Institute, University of Paris, Paris, France
| | - Thomas Guilbert
- IMAG'IC facility, Cochin Institute, Inserm U1016, CNRS UMR 8104, University of Paris UMR-S1016, Paris, France
| | - Philippe Burlet
- Department "Génétique Moléculaire," Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Jean-Michel Lapierre
- Department of "Histologie - Embryologie-Cytogénétique," Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | | | - Marc Le Lorc'H
- Department of "Histologie - Embryologie-Cytogénétique," Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Eric Vicaut
- Unité de Recherche Clinique, ACTION Study Group, Hôpital Fernand Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Kalliopi Chatzovoulou
- Department "Génétique Moléculaire," Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Institut Imagine, Université de Paris, Laboratoire des Maladies Génétiques Mitochondriales. Inserm UMR1163, Paris, France
| | - Julie Steffann
- Department "Génétique Moléculaire," Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Institut Imagine, Université de Paris, Laboratoire des Maladies Génétiques Mitochondriales. Inserm UMR1163, Paris, France
| | - Serge Romana
- Department of "Histologie - Embryologie-Cytogénétique," Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Institut Imagine, Université de Paris, Laboratoire d'Embryologie et de Génétique des Malformations Congénitales, Inserm UMR1163, Paris, France
| | - Céline Méhats
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France
| | - Piétro Santulli
- Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Catherine Patrat
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France; Department "Histologie-Embryologie-Biologie de la Reproduction," Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Daniel Vaiman
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France
| | - Ahmed Ziyyat
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France; Department "Histologie-Embryologie-Biologie de la Reproduction," Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Jean Philippe Wolf
- Team "From Gametes To Birth," Cochin Institute, Inserm U1016, CNRS UMR8104, Université de Paris, Paris, France; Department "Histologie-Embryologie-Biologie de la Reproduction," Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
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11
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Blythe EN, Weaver LC, Brown A, Dekaban GA. β2 Integrin CD11d/CD18: From Expression to an Emerging Role in Staged Leukocyte Migration. Front Immunol 2021; 12:775447. [PMID: 34858434 PMCID: PMC8630586 DOI: 10.3389/fimmu.2021.775447] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/08/2021] [Indexed: 12/12/2022] Open
Abstract
CD11d/CD18 is the most recently discovered and least understood β2 integrin. Known CD11d adhesive mechanisms contribute to both extravasation and mesenchymal migration – two key aspects for localizing peripheral leukocytes to sites of inflammation. Differential expression of CD11d induces differences in monocyte/macrophage mesenchymal migration including impacts on macrophage sub-set migration. The participation of CD11d/CD18 in leukocyte localization during atherosclerosis and following neurotrauma has sparked interest in the development of CD11d-targeted therapeutic agents. Whereas the adhesive properties of CD11d have undergone investigation, the signalling pathways induced by ligand binding remain largely undefined. Underlining each adhesive and signalling function, CD11d is under unique transcriptional control and expressed on a sub-set of predominately tissue-differentiated innate leukocytes. The following review is the first to capture the nearly three decades of CD11d research and discusses the emerging role of CD11d in leukocyte migration and retention during the progression of a staged immune response.
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Affiliation(s)
- Eoin N Blythe
- Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON, Canada.,Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
| | - Lynne C Weaver
- Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON, Canada.,Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
| | - Arthur Brown
- Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON, Canada.,Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada
| | - Gregory A Dekaban
- Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON, Canada.,Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
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12
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Ahmed S, Kim Y. PGE 2 mediates hemocyte-spreading behavior by activating aquaporin via cAMP and rearranging actin cytoskeleton via Ca 2. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2021; 125:104230. [PMID: 34388674 DOI: 10.1016/j.dci.2021.104230] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/04/2021] [Accepted: 08/08/2021] [Indexed: 06/13/2023]
Abstract
Spreading behavior of hemocytes (= insect blood cells) is essential for cellular immune responses against various microbial pathogens. It is activated by prostaglandin E2 (PGE2) via its membrane receptor associated with secondary messenger, cAMP, in insects. This study observed an increase of calcium ion (Ca2+) level after an acute increase of cAMP induced by PGE2 treatment and clarified the intracellular signals underlying the hemocyte-spreading behavior. Inhibition of Ca2+ flux significantly impaired the hemocyte-spreading and subsequent cellular immune response, phagocytosis. The up-regulation of intracellular Ca2+ in response to PGE2 was dependent on cAMP because RNA interference (RNAi) of PGE2 receptor expression or inhibiting adenylate cyclase prevented Ca2+ mobilization. The up-regulation of Ca2+ was induced by inositol triphosphate (IP3) via its specific IP3 receptor. Furthermore, inhibition of ryanodine receptor impaired Ca2+ mobilization, suggesting Ca2+-induced Ca2+ release. However, the effective spreading behavior of hemocytes was dependent on both secondary messengers. Ca2+ signal stimulated by cAMP was required for activating small G proteins because RNAi treatments of small G proteins such as Rac1, RhoA, and Cdc42 failed to stimulate hemocyte-spreading. In contrast, aquaporin was activated by cAMP. Its activity was necessary for changing cell volume during hemocyte-spreading. These results indicate that PGE2 mediates hemocyte-spreading via cAMP signal to activate aquaporin and via Ca2+ signal to activate actin cytoskeletal rearrangement.
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Affiliation(s)
- Shabbir Ahmed
- Department of Plant Medicals, Andong National University, Andong, 36729, South Korea
| | - Yonggyun Kim
- Department of Plant Medicals, Andong National University, Andong, 36729, South Korea.
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13
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Bieri M, Hendrickx R, Bauer M, Yu B, Jetzer T, Dreier B, Mittl PRE, Sobek J, Plückthun A, Greber UF, Hemmi S. The RGD-binding integrins αvβ6 and αvβ8 are receptors for mouse adenovirus-1 and -3 infection. PLoS Pathog 2021; 17:e1010083. [PMID: 34910784 PMCID: PMC8673666 DOI: 10.1371/journal.ppat.1010083] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Mammalian adenoviruses (AdVs) comprise more than ~350 types including over 100 human (HAdVs) and just three mouse AdVs (MAdVs). While most HAdVs initiate infection by high affinity/avidity binding of their fiber knob (FK) protein to either coxsackievirus AdV receptor (CAR), CD46 or desmoglein (DSG)-2, MAdV-1 (M1) infection requires arginine-glycine-aspartate (RGD) binding integrins. To identify the receptors mediating MAdV infection we generated five novel reporter viruses for MAdV-1/-2/-3 (M1, M2, M3) transducing permissive murine (m) CMT-93 cells, but not B16 mouse melanoma cells expressing mCAR, human (h) CD46 or hDSG-2. Recombinant M1 or M3 FKs cross-blocked M1 and M3 but not M2 infections. Profiling of murine and human cells expressing RGD-binding integrins suggested that αvβ6 and αvβ8 heterodimers are associated with M1 and M3 infections. Ectopic expression of mβ6 in B16 cells strongly enhanced M1 and M3 binding, infection, and progeny production comparable with mαvβ6-positive CMT-93 cells, whereas mβ8 expressing cells were more permissive to M1 than M3. Anti-integrin antibodies potently blocked M1 and M3 binding and infection of CMT-93 cells and hαvβ8-positive M000216 cells. Soluble integrin αvβ6, and synthetic peptides containing the RGDLXXL sequence derived from FK-M1, FK-M3 and foot and mouth disease virus coat protein strongly interfered with M1/M3 infections, in agreement with high affinity interactions of FK-M1/FK-M3 with αvβ6/αvβ8, determined by surface plasmon resonance measurements. Molecular docking simulations of ternary complexes revealed a bent conformation of RGDLXXL-containing FK-M3 peptides on the subunit interface of αvβ6/β8, where the distal leucine residue dips into a hydrophobic pocket of β6/8, the arginine residue ionically engages αv aspartate215, and the aspartate residue coordinates a divalent cation in αvβ6/β8. Together, the RGDLXXL-bearing FKs are part of an essential mechanism for M1/M3 infection engaging murine and human αvβ6/8 integrins. These integrins are highly conserved in other mammals, and may favour cross-species virus transmission.
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Affiliation(s)
- Manuela Bieri
- Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
- Molecular Life Sciences Graduate School, ETH and University Of Zurich, Switzerland
| | - Rodinde Hendrickx
- Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
- Molecular Life Sciences Graduate School, ETH and University Of Zurich, Switzerland
| | - Michael Bauer
- Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
| | - Bin Yu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China
| | - Tania Jetzer
- Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
| | - Birgit Dreier
- Department of Biochemistry, University of Zurich, Zurich, Switzerland
| | - Peer R. E. Mittl
- Department of Biochemistry, University of Zurich, Zurich, Switzerland
| | - Jens Sobek
- Functional Genomics Center Zurich, Eidgenössische Technische Hochschule (ETH) Zurich and University of Zurich, Zurich, Switzerland
| | - Andreas Plückthun
- Department of Biochemistry, University of Zurich, Zurich, Switzerland
| | - Urs F. Greber
- Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
| | - Silvio Hemmi
- Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
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14
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Significant differences in single-platelet biophysics exist across species but attenuate during clot formation. Blood Adv 2021; 5:432-437. [PMID: 33496738 DOI: 10.1182/bloodadvances.2020003755] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 12/06/2020] [Indexed: 12/14/2022] Open
Abstract
Key Points
Human, canine, ovine, and porcine platelets exhibit disparate biophysical signatures, whereas human and murine platelets are similar. Multiple biophysical parameters integrate during clot formation, measured by bulk clot contraction, and attenuate biophysical differences.
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15
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Li C, Zhang K, Pan G, Zhang L, Hu X, Zhao G, Deng C, Tan M, Li C, Xu M, Su J, Shen L, Kausar S, Yang L, Abbas MN, Cui H. Bmintegrin β1: A broadly expressed molecule modulates the innate immune response of Bombyx mori. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2021; 114:103869. [PMID: 32950537 DOI: 10.1016/j.dci.2020.103869] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 09/06/2020] [Accepted: 09/07/2020] [Indexed: 06/11/2023]
Abstract
Integrins are transmembrane glycoproteins that are broadly distributed in living organisms. As a heterodimer, they contain an α and a β subunit, which are reported to be associated with various physiological and pathological processes. In the present study, a 2502 bp full-length cDNA sequence of Bmintegrin β1 was obtained from the silkworm, Bombyx mori. Bmintegrin β1 belongs to the β subunit of the integrin family and contains several typical structures of integrins. Gene expression profile analysis demonstrated that Bmintegrin β1 was ubiquitously expressed in all tested tissues and organs, with the maximum expression levels in fat body and hemocytes. The immunofluorescence results showed that Bmintegrin β1 was located in the cell membrane and widely distributed in fat bodies and different types of hemocytes. Bmintegrin β1 expression was remarkably increased after challenging with different kinds of bacteria and pathogen-associated molecular patterns (PAMPs). Further investigation revealed that Bmintegrin β1 could participate in the agglutination of pathogenic bacteria possibly through direct binding with the relative bacteria and PAMPs. Altogether, this study provides a novel insight into the immune functional features of Bmintegrin β1.
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Affiliation(s)
- Chongyang Li
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Kui Zhang
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Guangzhao Pan
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Lei Zhang
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Xin Hu
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Gaichao Zhao
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Chaowei Deng
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Mengqin Tan
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Changhong Li
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Man Xu
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Jingjing Su
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Li Shen
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Saima Kausar
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Liqun Yang
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China
| | - Muhammad Nadeem Abbas
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China.
| | - Hongjuan Cui
- State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China; Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China; Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China.
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16
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Lv Z, Qiu L, Wang W, Liu Z, Liu Q, Wang L, Song L. The Members of the Highly Diverse Crassostrea gigas Integrin Family Cooperate for the Generation of Various Immune Responses. Front Immunol 2020; 11:1420. [PMID: 32793197 PMCID: PMC7390872 DOI: 10.3389/fimmu.2020.01420] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 06/02/2020] [Indexed: 12/25/2022] Open
Abstract
Studies on invertebrate immune receptors can provide insights into characteristics specific to innate immune system. Here, eight α and three β integrins are identified from an invertebrate, the Pacific oyster Crassostrea gigas, and their possible immune functions are studied. Oyster α/β integrins exhibit a higher degree of sequence and structural variability than the members from Homo sapiens and Drosophila melanogaster. The analysis reveals that oyster RGD- and laminin-binding receptor homologs are present in the phylogenetic tree of α integrins, but the other six oyster α integrins mainly form a species-specific branch; meanwhile, oyster β integrins are clustered with insect β integrins but distinct from a member from the mollusk Biomphalaria glabrata. Although phylogenetically lacking the important α integrin branches of LDV-binding, PS3-type, and αI-containing integrins, oyster integrins can bind to most ECM ligands, including RGDCP, LDVCP, GFOGERCP, and laminin protein in a distinct binding pattern. Besides, oyster integrins are distributed in different hemocyte subpopulations, while only specific integrins are selectively involved in hemocyte phagocytosis, migration, and encapsulation, and some of them participate in more than one immune response in a sophisticated pattern. Especially, oyster β integrins are arranged in the core to mediate complex immune responses, unlike the counterparts in humans that mainly depend on αI-containing integrins to incite immune reactions. This study represents the first comprehensive attempt to reveal the structural and evolutionary features of the integrin family and their involvement in cellular immune responses in the non-model invertebrate C. gigas and sheds light on the characteristics specific to the innate immune system in the integrin family.
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Affiliation(s)
- Zhao Lv
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.,University of Chinese Academy of Sciences, Beijing, China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China
| | - Limei Qiu
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China
| | - Weilin Wang
- Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.,Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.,Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, China
| | - Zhaoqun Liu
- Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.,Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.,Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, China
| | - Qing Liu
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China
| | - Lingling Wang
- Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.,Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.,Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, China
| | - Linsheng Song
- Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.,Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.,Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, China
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17
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Merle NS, Singh P, Rahman J, Kemper C. Integrins meet complement: The evolutionary tip of an iceberg orchestrating metabolism and immunity. Br J Pharmacol 2020; 178:2754-2770. [PMID: 32562277 PMCID: PMC8359198 DOI: 10.1111/bph.15168] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/27/2020] [Accepted: 05/29/2020] [Indexed: 12/18/2022] Open
Abstract
Immunologists have recently realized that there is more to the classic innate immune sensor systems than just mere protection against invading pathogens. It is becoming increasingly clear that such sensors, including the inflammasomes, toll-like receptors, and the complement system, are heavily involved in the regulation of basic cell physiological processes and particularly those of metabolic nature. In fact, their "non-canonical" activities make sense as no system directing immune cell activity can perform such task without the need for energy. Further, many of these ancient immune sensors appeared early and concurrently during evolution, particularly during the developmental leap from the single-cell organisms to multicellularity, and therefore crosstalk heavily with each other. Here, we will review the current knowledge about the emerging cooperation between the major inter-cell communicators, integrins, and the cell-autonomous intracellularly and autocrine-active complement, the complosome, during the regulation of single-cell metabolism. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.
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Affiliation(s)
- Nicolas S Merle
- Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Parul Singh
- Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Jubayer Rahman
- Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Claudia Kemper
- Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.,Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
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Maiorova MA, Satoh N, Khalturin K, Odintsova NA. Transcriptomic profiling of the mussel Mytilus trossulus with a special emphasis on integrin-like genes during development. INVERTEBR REPROD DEV 2019. [DOI: 10.1080/07924259.2019.1626774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Mariia A. Maiorova
- Laboratory of Cytotechnology, National Scientific Center of Marine Biology, The Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia
| | - Noriyuki Satoh
- Marine Genomcs Unit, Okinawa Institute Science & Technology, Okinawa, Japan
| | | | - Nelly A. Odintsova
- Laboratory of Cytotechnology, National Scientific Center of Marine Biology, The Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia
- Marine Invertebrate Biology Interfaculty Laboratory, Far Eastern Federal University, Vladivostok, Russia
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Zhu K, Takada Y, Nakajima K, Sun Y, Jiang J, Zhang Y, Zeng Q, Takada Y, Zhao M. Expression of integrins to control migration direction of electrotaxis. FASEB J 2019; 33:9131-9141. [PMID: 31116572 PMCID: PMC6662972 DOI: 10.1096/fj.201802657r] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Accepted: 04/15/2019] [Indexed: 02/05/2023]
Abstract
Proper control of cell migration is critically important in many biologic processes, such as wound healing, immune surveillance, and development. Much progress has been made in the initiation of cell migration; however, little is known about termination and sometimes directional reversal. During active cell migration, as in wound healing, development, and immune surveillance, the integrin expression profile undergoes drastic changes. Here, we uncovered the extensive regulatory and even opposing roles of integrins in directional cell migration in electric fields (EFs), a potentially important endogenous guidance mechanism. We established cell lines that stably express specific integrins and determined their responses to applied EFs with a high throughput screen. Expression of specific integrins drove cells to migrate to the cathode or to the anode or to lose migration direction. Cells expressing αMβ2, β1, α2, αIIbβ3, and α5 migrated to the cathode, whereas cells expressing β3, α6, and α9 migrated to the anode. Cells expressing α4, αV, and α6β4 lost directional electrotaxis. Manipulation of α9 molecules, one of the molecular directional switches, suggested that the intracellular domain is critical for the directional reversal. These data revealed an unreported role for integrins in controlling stop, go, and reversal activity of directional migration of mammalian cells in EFs, which might ensure that cells reach their final destination with well-controlled speed and direction.-Zhu, K., Takada, Y., Nakajima, K., Sun, Y., Jiang, J., Zhang, Y., Zeng, Q., Takada, Y., Zhao, M. Expression of integrins to control migration direction of electrotaxis.
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Affiliation(s)
- Kan Zhu
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
- Institute for Regenerative Cures, University of California–Davis, Sacramento, California, USA
- State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Surgery Research, Third Military Medical University, Chongqing, China
| | - Yoko Takada
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
| | - Kenichi Nakajima
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
- Institute for Regenerative Cures, University of California–Davis, Sacramento, California, USA
| | - Yaohui Sun
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
- Institute for Regenerative Cures, University of California–Davis, Sacramento, California, USA
| | - Jianxin Jiang
- State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Surgery Research, Third Military Medical University, Chongqing, China
| | - Yan Zhang
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
- Institute for Regenerative Cures, University of California–Davis, Sacramento, California, USA
- Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, China
| | - Qunli Zeng
- Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, China
| | - Yoshikazu Takada
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
| | - Min Zhao
- Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, California, USA
- Institute for Regenerative Cures, University of California–Davis, Sacramento, California, USA
- Department of Ophthalmology and Vision Science, School of Medicine, University of California–Davis, Sacramento, California, USA
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20
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Lv Z, Qiu L, Jia Z, Wang W, Liu Z, Wang L, Song L. The activated β-integrin (CgβV) enhances RGD-binding and phagocytic capabilities of hemocytes in Crassostrea gigas. FISH & SHELLFISH IMMUNOLOGY 2019; 87:638-649. [PMID: 30753917 DOI: 10.1016/j.fsi.2019.01.047] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 01/22/2019] [Accepted: 01/30/2019] [Indexed: 06/09/2023]
Abstract
Integrins are an important family of cell receptors that can bind foreign particles and promote cell phagocytosis after they are activated. In the present study, a novel β integrin was identified from pacific oyster Crassostrea gigas with an extracellular domain, a single transmembrane segment, and a short cytoplasmic domain. It was phylogenetically clustered with phagocytosis-related insecta βV, and designated as CgβV. CgβV shared a conserved NPX[Y/F] motif related to integrin activation with other phagocytosis-related β integrins. The mRNA transcripts of CgβV were widely detected in oyster tissues including hemocytes, gonad, adductor muscle, mantle, gill, and hepatopancreas, and the expression level in hemocytes was significantly up-regulated at 12 h after lipopolysaccharide (LPS) stimulation (p < 0.05), which was 2.29-fold higher than that in the control group. CgβV proteins were mainly observed on the hemocytes surface. The oyster hemocytes were found to bind fluorescein isothiocyanate (FITC)-labeled Arg-Gly-Asp-containing peptides (RGDCPs), and the binding capability was significantly up-regulated with the peak percentage of 37.6% at 12 h post LPS stimulation, which was higher than that in the control group (8.8%, p < 0.05), suggesting the activation of RGD-binding integrins on oyster hemocytes surface. The label-free RGDCPs and anti-CgβV antibody inhibited the binding capability of hemocytes towards FITC-labeled RGDCPs, which were significant lower in RGD blocking group (7.4%, p < 0.05) and anti-CgβV blocking group (22.1%, p < 0.05) than that in the control group (37.6%), indicating that CgβV could be a RGD-binding integrin. Phagocytosis assay demonstrated that LPS could enhance the phagocytosis of hemocytes towards Escherichia coli and fluorescent beads with the phagocytic rate (PR) of 18.3% and 17.4%, and phagocytic index (PI) of 5.29 and 37.71, respectively, which were significant higher than that in the control group (11.0% and 3.65 for E. coli, 9.8% and 29.26 for fluorescent beads, respectively, p < 0.05). In addition, both the label-free RGDCPs and anti-CgβV antibody significantly hindered the phagocytosis of hemocytes towards E. coli and fluorescent beads. After the E. coli and fluorescent beads were opsonized by oyster serum, the label-free RGDCPs still inhibited the phagocytosis of hemocytes towards them, while the anti-CgβV antibody could only inhibit the phagocytosis of hemocytes towards E. coli, suggesting that only the activated CgβV was involved in the enhancing phagocytosis for bacteria in oyster. Moreover, the key components of conserved integrin-mediated phagocytosis pathway including GTPases, talin proteins, Ca2+ and cAMP were all induced by LPS in hemocytes of oyster. All these results suggested that the activated CgβV enhanced RGD-binding and phagocytic capabilities of hemocytes, shedding lights on the mechanisms of integrin-mediated phagocytosis in mollusks.
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Affiliation(s)
- Zhao Lv
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Limei Qiu
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China
| | - Zhihao Jia
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Weilin Wang
- Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China
| | - Zhaoqun Liu
- Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China
| | - Lingling Wang
- Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China
| | - Linsheng Song
- Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China.
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Harryman WL, Warfel NA, Nagle RB, Cress AE. The Tumor Microenvironments of Lethal Prostate Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1210:149-170. [PMID: 31900909 DOI: 10.1007/978-3-030-32656-2_8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Localized prostate cancer (confined to the gland) generally is considered curable, with nearly a 100% 5-year-survival rate. When the tumor escapes the prostate capsule, leading to metastasis, there is a poorer prognosis and higher mortality rate, with 5-year survival dropping to less than 30%. A major research question has been to understand the transition from indolent (low risk) disease to aggressive (high risk) disease. In this chapter, we provide details of the changing tumor microenvironments during prostate cancer invasion and their role in the progression and metastasis of lethal prostate cancer. Four microenvironments covered here include the muscle stroma, perineural invasion, hypoxia, and the role of microvesicles in altering the extracellular matrix environment. The adaptability of prostate cancer to these varied microenvironments and the cues for phenotypic changes are currently understudied areas. Model systems for understanding smooth muscle invasion both in vitro and in vivo are highlighted. Invasive human needle biopsy tissue and mouse xenograft tumors both contain smooth muscle invasion. In combination, the models can be used in an iterative process to validate molecular events for smooth muscle invasion in human tissue. Understanding the complex and interacting microenvironments in the prostate holds the key to early detection of high-risk disease and preventing tumor invasion through escape from the prostate capsule.
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Affiliation(s)
| | - Noel A Warfel
- University of Arizona Cancer Center, Tucson, AZ, USA
| | - Raymond B Nagle
- Department of Pathology, University of Arizona Cancer Center, Tucson, AZ, USA
| | - Anne E Cress
- University of Arizona Cancer Center, Tucson, AZ, USA.
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22
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Tang X, Zhai F, Sheng X, Xing J, Zhan W. The Roles of β-Integrin of Chinese Shrimp (Fenneropenaeus chinensis) in WSSV Infection. Int J Mol Sci 2017; 18:ijms18071465. [PMID: 28686185 PMCID: PMC5535956 DOI: 10.3390/ijms18071465] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 06/28/2017] [Accepted: 07/03/2017] [Indexed: 01/21/2023] Open
Abstract
Our previous study demonstrated that an integrin β subunit of Chinese shrimp (Fenneropenaeus chinensis) (FcβInt) plays an important role in white spot syndrome virus (WSSV) infection. In the present work, in order to further elucidate the potential role of FcβInt in WSSV infection, the recombinant extracellular domain of β integringene of F. Chinensis (rFcβInt-ER) was expressed in Escherichia coli BL21 (DE3), and the eukaryotic expression plasmid PcDNA3.1-FcβInt-ER (PFcβInt-ER) was also constructed. Far-western blotting was performed to determine the binding specificity of rFcβInt-ER to WSSV envelope proteins, and results showed that rFcβInt-ER was able to specifically interact with rVP31, rVP37, rVP110 and rVP187. Moreover, the blocking effects of mouse anti-rFcβint-ER antibodies were both detected in vivo and in vitro. The ELISA and Dot-blotting in vitro assays both showed that mouse anti-rFcβInt-ER antibodies could partially block the binding of WSSV to the hemocyte membrane of F. chinensis. In the in vivo assays, the mortality of shrimp injected with WSSV mixed with anti-rFcβInt-ER antibodies was delayed, and was lower than in the control group. While the shrimp were intramuscularly injected with PFcβInt-ER, transcripts of PFcβInt-ER could be detected in different shrimp tissues within 7 days, and the mortality of shrimp injected with PFcβInt-ER was also delayed and lower compared with the control group post WSSV challenge. Furthermore, gene silencing technology was also used to verify the effect of FcβInt in WSSV infection, and results showed that the expression levels of the WSSV immediate early gene iel, early gene wsv477, and late gene VP28 and the mortality of F. Chinensis were all significantly decreased in the FcβInt knock-down hemocyctes compared to the control group. Taken together, these results suggest that FcβInt plays important roles in WSSV infection.
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Affiliation(s)
- Xiaoqian Tang
- Laboratory of Pathology and Immunology of Aquatic Animals, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, No. 1 Wenhai Road, Aoshanwei Town, Jimo, Qingdao 266071, China.
| | - Fude Zhai
- Laboratory of Pathology and Immunology of Aquatic Animals, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
| | - Xiuzhen Sheng
- Laboratory of Pathology and Immunology of Aquatic Animals, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
| | - Jing Xing
- Laboratory of Pathology and Immunology of Aquatic Animals, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
| | - Wenbin Zhan
- Laboratory of Pathology and Immunology of Aquatic Animals, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, No. 1 Wenhai Road, Aoshanwei Town, Jimo, Qingdao 266071, China.
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Anjos L, Morgado I, Guerreiro M, Cardoso JCR, Melo EP, Power DM. Cartilage acidic protein 1, a new member of the beta-propeller protein family with amyloid propensity. Proteins 2016; 85:242-255. [DOI: 10.1002/prot.25210] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Revised: 11/06/2016] [Accepted: 11/09/2016] [Indexed: 12/22/2022]
Affiliation(s)
- Liliana Anjos
- Comparative Endocrinology and Integrative Biology Group (CEIB), Centro de Ciencias do Mar (CCMAR), University of Algarve; Campus de Gambelas Faro 8005-139 Portugal
| | - Isabel Morgado
- Comparative Endocrinology and Integrative Biology Group (CEIB), Centro de Ciencias do Mar (CCMAR), University of Algarve; Campus de Gambelas Faro 8005-139 Portugal
| | - Marta Guerreiro
- Comparative Endocrinology and Integrative Biology Group (CEIB), Centro de Ciencias do Mar (CCMAR), University of Algarve; Campus de Gambelas Faro 8005-139 Portugal
| | - João C. R. Cardoso
- Comparative Endocrinology and Integrative Biology Group (CEIB), Centro de Ciencias do Mar (CCMAR), University of Algarve; Campus de Gambelas Faro 8005-139 Portugal
| | - Eduardo P. Melo
- Campus de Gambelas, Center for Biomedical Research, University of Algarve; Faro 8005-139 Portugal
| | - Deborah M. Power
- Comparative Endocrinology and Integrative Biology Group (CEIB), Centro de Ciencias do Mar (CCMAR), University of Algarve; Campus de Gambelas Faro 8005-139 Portugal
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Abbasi AA. Diversification of four human HOX gene clusters by step-wise evolution rather than ancient whole-genome duplications. Dev Genes Evol 2015; 225:353-7. [PMID: 26481129 DOI: 10.1007/s00427-015-0518-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 10/08/2015] [Indexed: 12/30/2022]
Abstract
HOX genes encode transcriptional factors that play a pivotal role in specifying regional identity in nearly every bilateral animal. The birth of HOX gene cluster and its subsequent evolution, either in regulation or function, underlie the evolution of many bilaterian features and hence to the evolutionary radiation of this group. Despite of this importance, evolution of HOX cluster in vertebrates remains largely obscure because the phylogenetic history of these genes is poorly resolved. This has led to the controversy about whether four HOX clusters in human originated through two rounds (2R) of whole-genome duplications or instead evolved by small-scale events early in vertebrate evolution. Recently, the large-scale phylogenetic analysis of triplicate and quadruplicate paralogous regions residing on human HOX-bearing chromosomes provided an unprecedented insight into events that shaped vertebrate genome early in their history. Based on these data and comparative genomic analysis of fruit fly, red floor beetle, and human, this study infers the genic content of minimal HOX locus in the Urbilaterian and reconstructs its duplication history. It appears that four HOX clusters of humans are not remnants of polyploidy events in vertebrate ancestry. Rather, current evidence suggests that one-to-four transition in HOX cluster number occurred by three-step sequential process involving regional duplication events. Therefore, it is concluded that the evolutionary origin of vertebrate novelties, including the complexity of their body, is the consequence of small-scale genetic changes at widely different times over their history.
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Affiliation(s)
- Amir Ali Abbasi
- National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
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Huang Y, Zhao LL, Feng JL, Zhu HX, Huang X, Ren Q, Wang W. A novel integrin function in innate immunity from Chinese mitten crab (Eriocheir sinensis). DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2015; 52:155-165. [PMID: 26004499 DOI: 10.1016/j.dci.2015.05.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 05/15/2015] [Accepted: 05/18/2015] [Indexed: 06/04/2023]
Abstract
Integrins belong to a superfamily of conserved α β heterodimeric cell surface receptors that have critical function in cell migration, differentiation, and survival. In this study, an integrin called EsIntegrin was identified from Chinese mitten crab Eriocheir sinensis. EsIntegrin cDNA is 4415 bp long with a 2457 bp open reading frame that encodes an 818 amino acid protein. EsIntegrin contains a signal peptide, an integrin beta subunit (N-terminal portion of extracellular region) INB domain, an epidermal growth factor (hEGF) domain, an integrin B tail domain, a transmembrane region, and an integrin b cyt domain. EsIntegrin was mainly expressed in hemocytes and the heart, with a relatively lower expression level in gills, nerves, intestine, hepatopancreas, muscles, and eyestalk. When healthy crabs were challenged with LPS, PGN, Staphyloccocus aureus, or Vibrio parahaemolyticus, EsIntegrin expression level was upregulated significantly. Recombinant EsIntegrin has agglutination activity to Gram-positive (e.g., S. aureus and Bacillus subtilis) and Gram-negative bacteria (e.g., V. parahaemolyticus and Aeromonas hydrophila) in the presence of calcium. Furthermore, rEsIntegrin could not only bind to various bacteria such as S. aureus, Micrococcus luteus, B. subtilis, Bacillus megaterium, Bacillus thuringiensis, V. parahaemolyticus, Vibrio anguillarum, A. hydrophila, Vibrio natriegens, and Escherichia coli, but this compound also helped crabs in clearing virulent Gram-negative bacterium, V. parahaemolyticus, in vivo. These data suggested that EsIntegrin might function as cellular receptor that is involved in anti-bacterial immunity from E. sinensis.
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Affiliation(s)
- Ying Huang
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China
| | - Ling-Ling Zhao
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China
| | - Jin-Ling Feng
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China
| | - Huan-Xi Zhu
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China
| | - Xin Huang
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China
| | - Qian Ren
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China.
| | - Wen Wang
- Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, China.
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Sabetian S, Shamsir MS. Identification of putative drug targets for human sperm-egg interaction defect using protein network approach. BMC SYSTEMS BIOLOGY 2015; 9:37. [PMID: 26187737 PMCID: PMC4506605 DOI: 10.1186/s12918-015-0186-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 07/06/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND Sperm-egg interaction defect is a significant cause of in-vitro fertilization failure for infertile cases. Numerous molecular interactions in the form of protein-protein interactions mediate the sperm-egg membrane interaction process. Recent studies have demonstrated that in addition to experimental techniques, computational methods, namely protein interaction network approach, can address protein-protein interactions between human sperm and egg. Up to now, no drugs have been detected to treat sperm-egg interaction disorder, and the initial step in drug discovery research is finding out essential proteins or drug targets for a biological process. The main purpose of this study is to identify putative drug targets for human sperm-egg interaction deficiency and consider if the detected essential proteins are targets for any known drugs using protein-protein interaction network and ingenuity pathway analysis. RESULTS We have created human sperm-egg protein interaction networks with high confidence, including 106 nodes and 415 interactions. Through topological analysis of the network with calculation of some metrics, such as connectivity and betweenness centrality, we have identified 13 essential proteins as putative drug targets. The potential drug targets are from integrins, fibronectins, epidermal growth factor receptors, collagens and tetraspanins protein families. We evaluated these targets by ingenuity pathway analysis, and the known drugs for the targets have been detected, and the possible effective role of the drugs on sperm-egg interaction defect has been considered. These results showed that the drugs ocriplasmin (Jetrea©), gefitinib (Iressa©), erlotinib hydrochloride (Tarceva©), clingitide, cetuximab (Erbitux©) and panitumumab (Vectibix©) are possible candidates for efficacy testing for the treatment of sperm-egg interaction deficiency. Further experimental validation can be carried out to confirm these results. CONCLUSION We have identified the first potential list of drug targets for human sperm-egg interaction defect using the protein interaction network approach. The essential proteins or potential drug targets were found using topological analysis of the protein network. These putative targets are promising for further experimental validation. These study results, if validated, may develop drug discovery techniques for sperm-egg interaction defect and also improve assisted reproductive technologies to avoid in-vitro fertilization failure.
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Affiliation(s)
- Soudabeh Sabetian
- Department of Biosciences and Health Sciences, Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Johor, Malaysia.
| | - Mohd Shahir Shamsir
- Department of Biosciences and Health Sciences, Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Johor, Malaysia.
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Dyachuk VA, Maiorova MA, Odintsova NA. Identification of β integrin-like- and fibronectin-like proteins in the bivalve mollusk Mytilus trossulus. Dev Growth Differ 2015; 57:515-28. [PMID: 26183371 DOI: 10.1111/dgd.12234] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 06/04/2015] [Accepted: 06/14/2015] [Indexed: 01/28/2023]
Abstract
Integrins play a key role in the intermediation and coordination between cells and extracellular matrix components. In this study, we first determined the presence of the β integrin-like protein and its presumptive ligand, fibronectin-like protein, during development and in some adult tissues of the bivalve mollusc Mytilus trossulus. We found that β integrin-like protein expression correlated with the development and differentiation of the digestive system in larvae. Besides the presence of β integrin-like protein in the digestive epithelial larval cells, this protein was detected in the hemocytes and some adult tissues of M. trossulus. The fibronectin-like protein was detected firstly at the blastula stage and later, the FN-LP-immunoreactive cells were scattered in the trochophore larvae. The fibronectin-like protein was not expressed in the β integrin-positive cells of either the veliger stage larvae or the adult mussel tissues and the primary hemocyte cell culture. Despite the β integrin- and fibronectin-like proteins being expressed in different cell types of mussel larvae, we do not exclude the possibility of direct interaction between these two proteins during M. trossulus development or in adult tissues.
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Affiliation(s)
- Vyacheslav A Dyachuk
- A. V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the Russian Academy of Sciences, Palchevsky Str. 17, 690041, Vladivostok, Russia.,Far Eastern Federal University, 690950, Vladivostok, Russia
| | - Maria A Maiorova
- A. V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the Russian Academy of Sciences, Palchevsky Str. 17, 690041, Vladivostok, Russia.,Far Eastern Federal University, 690950, Vladivostok, Russia
| | - Nelly A Odintsova
- A. V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the Russian Academy of Sciences, Palchevsky Str. 17, 690041, Vladivostok, Russia.,Far Eastern Federal University, 690950, Vladivostok, Russia
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28
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Zhang X, Song YF, Lu HN, Wang DP, Zhang XS, Huang SL, Sun BL, Huang ZG. Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas. World J Gastroenterol 2015; 21:2629-2637. [PMID: 25759530 PMCID: PMC4351212 DOI: 10.3748/wjg.v21.i9.2629] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Revised: 10/31/2014] [Accepted: 12/01/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate GATA5, SFRP2, and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer (CRC) or adenomas.
METHODS: There were 57 CRC patients, 30 adenomas patients, and 47 control patients enrolled in this study. Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5, SFRP2, and ITGA4 genes in plasma DNA, and their association with clinical outcome in CRC. The predictive ability of GATA5, SFRP2, and ITGA4 methylation, individually or in combination, to detect CRC or adenomas was further analyzed.
RESULTS: Hypermethylated GATA5 was detected in plasma in 61.4% (35/57) of CRC cases, 43.33% (13/30) of adenoma cases, and 21.28% (10/47) of control cases. The hypermethylation of SFRP2 was detected in 54.39% (31/57), 40.00% (12/30), and 27.66% (13/47) in plasma samples from CRC, adenomas, and controls, respectively. ITGA4 methylation was detected in 36.84% (21/57) of plasma samples of CRC patients and in 30.00% (9/30) of plasma samples from patients with colorectal adenomas, and the specificity of this individual biomarker was 80.85% (9/47). Moreover, GATA5 methylation in the plasma was significantly correlated with larger tumor size (P = 0.019), differentiation status (P = 0.038), TNM stage (P = 0.008), and lymph node metastasis (P = 0.008). SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status (SFRP2, P = 0.012; ITGA4, P = 0.007), TNM stage (SFRP2, P = 0.034; ITGA4, P = 0.021), and lymph node metastasis (SFRP2, P = 0.034; ITGA4, P = 0.021). From the perspective of predictive power and cost-performance, using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC (OR = 8.06; 95%CI: 2.54-25.5; P < 0.01) and adenomas (OR = 3.35; 95%CI: 1.29-8.71; P = 0.012).
CONCLUSION: A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.
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Maiorova MA, Odintsova NA. β Integrin-like protein-mediated adhesion and its disturbances during cell cultivation of the mussel Mytilus trossulus. Cell Tissue Res 2015; 361:581-92. [PMID: 25673210 DOI: 10.1007/s00441-015-2122-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Accepted: 01/13/2015] [Indexed: 01/09/2023]
Abstract
In this study, we focus on the specific contribution of β integrin-like protein to adhesion-mediated events in molluscan larval cells in culture that could not have been investigated within the whole animal. An analysis of disturbances to cell-substratum adhesion, caused by the integrin receptor inhibiting Arg-Gly-Asp-Ser (RGDS)-peptide, the Ca(2+)/Mg(2+)-chelators and the stress influence of freezing-thawing, reveals that all these factors resulted in the partial destruction of the integrin-extracellular matrix (ECM) interaction in culture and, in particular, changes in the distribution and relative abundance of β integrin-positive cells. The experiments, carried out on selected substrates, found that β integrin-positive cells demonstrate different affinities for the substrates. This finding further supports the assumption that epithelial differentiation in cultivated cells of larval Mytilus may be mediated by β integrin-like proteins via binding to laminin; direct binding to other components of the ECM could not be demonstrated. The mussel β integrin-positive cells are not involved in myogenic or neuronal differentiation on any of the substrates but part of them has tubulin-positive cilia, forming some epithelia-like structures. Our data indicate that β integrin-positive cells are able to proliferate in vitro which suggests that they could participate in renewing the digestive epithelium in larvae. The findings provide evidence that the distribution pattern of β integrin-like protein depends on the cell type and the factors influencing the adhesion.
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Affiliation(s)
- Mariia A Maiorova
- A. V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the Russian Academy of Sciences, Palchevsky Str. 17, 690041, Vladivostok, Russia
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Chouhan BS, Käpylä J, Denessiouk K, Denesyuk A, Heino J, Johnson MS. Early chordate origin of the vertebrate integrin αI domains. PLoS One 2014; 9:e112064. [PMID: 25409021 PMCID: PMC4237329 DOI: 10.1371/journal.pone.0112064] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 10/11/2014] [Indexed: 12/17/2022] Open
Abstract
Half of the 18 human integrins α subunits have an inserted αI domain yet none have been observed in species that have diverged prior to the appearance of the urochordates (ascidians). The urochordate integrin αI domains are not human orthologues but paralogues, but orthologues of human αI domains extend throughout later-diverging vertebrates and are observed in the bony fish with duplicate isoforms. Here, we report evidence for orthologues of human integrins with αI domains in the agnathostomes (jawless vertebrates) and later diverging species. Sequence comparisons, phylogenetic analyses and molecular modeling show that one nearly full-length sequence from lamprey and two additional fragments include the entire integrin αI domain region, have the hallmarks of collagen-binding integrin αI domains, and we show that the corresponding recombinant proteins recognize the collagen GFOGER motifs in a metal dependent manner, unlike the α1I domain of the ascidian C. intestinalis. The presence of a functional collagen receptor integrin αI domain supports the origin of orthologues of the human integrins with αI domains prior to the earliest diverging extant vertebrates, a domain that has been conserved and diversified throughout the vertebrate lineage.
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Affiliation(s)
- Bhanupratap Singh Chouhan
- Structural Bioinformatics Laboratory, Biochemistry, Department of Biosciences, Åbo Akademi University, Turku, Finland
| | - Jarmo Käpylä
- Department of Biochemistry, University of Turku, Turku, Finland
| | - Konstantin Denessiouk
- Structural Bioinformatics Laboratory, Biochemistry, Department of Biosciences, Åbo Akademi University, Turku, Finland
| | - Alexander Denesyuk
- Structural Bioinformatics Laboratory, Biochemistry, Department of Biosciences, Åbo Akademi University, Turku, Finland
| | - Jyrki Heino
- Department of Biochemistry, University of Turku, Turku, Finland
| | - Mark S. Johnson
- Structural Bioinformatics Laboratory, Biochemistry, Department of Biosciences, Åbo Akademi University, Turku, Finland
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Park Y, Ahn SJ, Vogel H, Kim Y. Integrin β subunit and its RNA interference in immune and developmental processes of the Oriental tobacco budworm, Helicoverpa assulta. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2014; 47:59-67. [PMID: 25008242 DOI: 10.1016/j.dci.2014.06.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 06/26/2014] [Accepted: 06/28/2014] [Indexed: 06/03/2023]
Abstract
Integrins are cell surface heterodimeric proteins interacting with the extracellular matrix and mediating environmental signals through cell membranes. A full-length cDNA sequence of the integrin β1 subunit gene (HaITGb1) was cloned from the Oriental tobacco budworm, Helicoverpa assulta, and analyzed for its physiological role in both immune response and development. HaITGb1 was expressed in all developmental stages from egg to adult and in all tested larval tissues of hemocytes, fat body, gut, and epidermis. Utilizing an RNA interference (RNAi) approach, injection of a specific double-stranded RNA (dsRNA) in larvae suppressed HaITGb1 transcript levels and significantly impaired hemocytes in their extracellular matrix adherence properties. Furthermore, the RNAi treatment significantly suppressed hemocyte nodule formation in response to bacterial challenge, which resulted in significantly enhanced susceptibility to both pathogenic and non-pathogenic bacteria. The RNAi treatment also interfered with H. assulta larval and pupal development. These results suggest that the extensive and constitutive expression of HaITGb1 is necessary for H. assulta to perform an efficient immune response against microbial pathogens and undergo normal immature development.
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Affiliation(s)
- Youngjin Park
- Department of Bioresource Sciences, Andong National University, Andong 760-749, Republic of Korea
| | - Seung-Joon Ahn
- Department of Entomology, Max Planck Institute for Chemical Ecology, Jena 07745, Germany
| | - Heiko Vogel
- Department of Entomology, Max Planck Institute for Chemical Ecology, Jena 07745, Germany
| | - Yonggyun Kim
- Department of Bioresource Sciences, Andong National University, Andong 760-749, Republic of Korea.
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Zhang K, Xu M, Su J, Yu S, Sun Z, Li Y, Zhang W, Hou J, Shang L, Cui H. Characterization and identification of the integrin family in silkworm, Bombyx mori. Gene 2014; 549:149-55. [DOI: 10.1016/j.gene.2014.07.060] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 07/13/2014] [Accepted: 07/23/2014] [Indexed: 11/29/2022]
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Dong YW, Wang R, Cai QQ, Qi B, Wu W, Zhang YH, Wu XZ. Sulfatide epigenetically regulates miR-223 and promotes the migration of human hepatocellular carcinoma cells. J Hepatol 2014; 60:792-801. [PMID: 24333181 DOI: 10.1016/j.jhep.2013.12.004] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 11/22/2013] [Accepted: 12/02/2013] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS The biological relevance and regulation mechanism of aberrant miR-223 expression in human hepatocellular carcinoma (HCC) remain unknown. Our aim was to investigate miR-223 regulation in HCC. METHODS miR-223 and integrin αV dysregulation were verified in 57 HCC specimens. Immunohistochemical analysis of integrin αV and sulfatide levels was performed on another cohort of 103 HCC samples. Epigenetic analysis was used to explore the effect of sulfatide on miR-223 transcription. Orthotopic growth, and intrahepatic and pulmonary metastasis of tumors derived from SMMC-7721 cells expressing miR-223 or cerebroside sulfotransferase were monitored in mice. RESULTS miR-223 was reduced in HCC specimens and highly metastatic cell lines. Enhanced miR-223 expression had a negative effect on integrin αV-mediated cell migration. In vivo assays of metastasis in an orthotopically implanted model demonstrated that miR-223 effectively inhibited HCC metastasis. Further analysis demonstrated that integrin αV is negatively regulated by miR-223. Moreover, the integrin αV subunit was significantly positively correlated with highly expressed sulfatide in 103 HCC specimens. Intriguingly, miR-223 expression was suppressed by sulfatide in HCC in association with reduced recruitment of acetylated histone H3 and C/EBPα to the pre-miR-223 gene promoter, where monocytic leukemia zinc finger (MOZ) protein, a MYST-type histone acetyltransferase, lost its attachment. The expression of histone deacetylases, HDAC9 and HDAC10, were greatly stimulated by sulfatide and their recruitment to miR-223 gene promoter was enhanced. CONCLUSIONS Downregulation of miR-223 in HCC is associated with the epigenetic regulation by highly expressed sulfatide and involved in tumor metastasis.
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MESH Headings
- Animals
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Cell Line, Tumor
- Cell Movement
- Down-Regulation
- Epigenesis, Genetic
- Gene Expression Regulation, Neoplastic
- Heterografts
- Humans
- Integrin alphaV/genetics
- Integrin alphaV/metabolism
- Liver Neoplasms/genetics
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Mice
- Mice, Nude
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Neoplasm Metastasis
- Promoter Regions, Genetic
- RNA, Neoplasm/genetics
- RNA, Neoplasm/metabolism
- Sulfoglycosphingolipids/metabolism
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Affiliation(s)
- Yi Wei Dong
- Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China
| | - Rong Wang
- Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China
| | - Qian Qian Cai
- Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China
| | - Bing Qi
- Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China
| | - Wei Wu
- Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China
| | - Yong Hu Zhang
- People's Hospital of Beilun District, Ningbo, Zhejiang, China
| | - Xing Zhong Wu
- Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China.
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Abstract
In humans, an ~200-residue "inserted" I domain, a von Willebrand factor A domain (vWFA), buds out from the β-propeller domain in 9 of 18 integrin α subunits. The vWFA domain is not unique to the α subunit as it is an integral part of all integrin β subunits and many other proteins. The βI domain has always been a component of integrins but the αI domain makes its appearance relatively late, in early chordates, since it is found in tunicates and later diverging species. The tunicate αI domains are distinct from the human collagen and leukocyte recognizing integrin α subunits, but fragments of integrins from agnathastomes suggest that the human-type αI domains arose in an ancestor of the very first vertebrate species. The rise of integrins with αI domains parallels the enormous changes in body plan and systemic development of the chordate line that began some 550 million or more years ago.
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Park J, Stanley D, Kim Y. Rac1 mediates cytokine-stimulated hemocyte spreading via prostaglandin biosynthesis in the beet armyworm, Spodoptera exigua. JOURNAL OF INSECT PHYSIOLOGY 2013; 59:682-689. [PMID: 23660478 DOI: 10.1016/j.jinsphys.2013.04.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Revised: 04/09/2013] [Accepted: 04/24/2013] [Indexed: 06/02/2023]
Abstract
Cell spreading is an integral component of insect hemocytic immune reactions to infections and invasions. Cell spreading is accomplished by cytoskeleton rearrangement, which is activated by three major immune mediators, biogenic monoamines, plasmatocyte-spreading peptide (PSP), and eicosanoids, particularly prostaglandin E2 (PGE2). However, little is known about how these immune mediators activate hemocyte spreading at the intra-cellular level. A small G protein, Rac1, acts in cytoskeleton arrangements in mammalian cells. Based on this information, we identified a Rac1 transcript (SeRac1) in hemocytes prepared from Spodoptera exigua. SeRac1 was expressed in most developmental stages and in the two main immunity-conferring tissues, hemocytes and fat body, in larvae. In response to bacterial challenge, its expression was up-regulated by >37-fold at 2h post-injection and returned to a basal level about 2h later. Silencing SeRac1 expression inhibited hemocyte spreading in response to three immune mediators, octopamine, 5-hydroxytryptamine, and PSP. Addition of PGE2 to SeRac1-silenced larvae rescued the influence of these three mediators on hemocyte spreading. These compounds also increased phospholipase A2 activity via SeRac1, which leads to prostaglandin biosynthesis. We infer that SeRac1 transduces OA, 5-HT, and PSP signaling via activating biosynthesis of prostaglandins and possibly other eicosanoids.
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Affiliation(s)
- Jiyeong Park
- Department of Bioresource Sciences, Andong National University, Andong 760-749, Republic of Korea
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Cartilage Acidic Protein 2 a hyperthermostable, high affinity calcium-binding protein. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 2013; 1834:642-50. [DOI: 10.1016/j.bbapap.2012.12.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Revised: 12/14/2012] [Accepted: 12/18/2012] [Indexed: 01/27/2023]
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Discovery of platyhelminth-specific α/β-integrin families and evidence for their role in reproduction in Schistosoma mansoni. PLoS One 2012; 7:e52519. [PMID: 23300694 PMCID: PMC3531407 DOI: 10.1371/journal.pone.0052519] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Accepted: 11/15/2012] [Indexed: 12/17/2022] Open
Abstract
In all metazoa, the response of cells to molecular stimuli from their environment represents a fundamental principle of regulatory processes controlling cell growth and differentiation. Among the membrane-linked receptors mediating extracellular communication processes are integrin receptors. Besides managing adhesion to the extracellular matrix or to other cells, they arrange information flow into the cells by activating intracellular signaling pathways often acting synergistically through cooperation with growth factor receptors. Although a wealth of information exists on integrins in different model organisms, there is a big gap of knowledge for platyhelminths. Here we report on the in silico detection and reconstruction of α and β integrins from free-living and parasitic platyhelminths, which according to structural and phylogenetic analyses form specific clades separate from each other and from further metazoan integrins. As representative orthologs of parasitic platyhelminths we have cloned one beta-integrin (Smβ-Int1) and four alpha-integrins (Smα-Int1 - Smα-Int4) from Schistosoma mansoni; they were characterized by molecular and biochemical analyses. Evidence is provided that Smβ-Int1 interacts and co-localizes in the reproductive organs with known schistosome cellular tyrosine kinases (CTKs), of which the Syk kinase SmTK4 appeared to be the strongest interaction partner as shown by yeast two-hybrid analyses and coimmunoprecipitation experiments. By a novel RNAi approach with adult schistosomes in vitro we demonstrate for the first time multinucleated oocytes in treated females, indicating a decisive role Smβ-Int1 during oogenesis as phenotypically analyzed by confocal laser scanning microscopy (CLSM). Our findings provide a first comprehensive overview about platyhelminth integrins, of which the parasite group exhibits unique features allowing a clear distinction from the free-living groups. Furthermore, we shed first lights on the functions of integrins in a trematode model parasite, revealing the complexity of molecular processes involved in its reproductive biology, which may be representative for other platyhelminths.
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Localization of αvβ3-like integrin in cultivated larval cells of the mussel Mytilus trossulus during neuronal and muscle differentiation. J Mol Histol 2012; 43:449-59. [PMID: 22673772 DOI: 10.1007/s10735-012-9428-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Accepted: 05/24/2012] [Indexed: 12/28/2022]
Abstract
Using immunofluorescence phenotyping, the expression of αvβ3-like integrin was examined during neuronal and muscle differentiation in cell cultures derived from trochophore larvae of the mussel Mytilus trossulus. We have demonstrated that some mussel cells grown on fibronectin in vitro express the extracellular matrix (ECM) αvβ3 integrin-like receptor. At the same time, the distribution of αvβ3-like integrin is not ubiquitous, i.e. it depends on the cell type and the time of cultivation. Using immunohistochemical staining, we have found that only in some cells this integrin is co-localized with molluscan neuronal markers, neurotransmitters serotonin (5-HT) or Phe-Met-Arg-Phe-NH(2) neuropeptide (FMRFamide), and also with filament actin but not with paramyosin. Although we have previously shown that an integrin-dependent mechanism is involved in cell adhesion and differentiation of muscle cells of Mytilus, in this study, αvβ3-like integrin has not been found to participate in fibronectin adhesion of muscle cells but may be a linking agent between the ECM and the neuron-like cells.
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Papagiannouli F, Lohmann I. Shaping the niche: lessons from the Drosophila testis and other model systems. Biotechnol J 2012; 7:723-36. [PMID: 22488937 DOI: 10.1002/biot.201100352] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 01/31/2012] [Accepted: 02/27/2012] [Indexed: 11/12/2022]
Abstract
Stem cells are fascinating, as they supply the cells that construct our adult bodies and replenish, as we age, worn out, damaged, and diseased tissues. Stem cell regulation relies on intrinsic signals but also on inputs emanating from the neighbouring niche. The Drosophila testis provides an excellent system for studying such processes. Although recent advances have uncovered several signalling, cytoskeletal and other factors affecting niche homeostasis and testis differentiation, many aspects of niche regulation and maintenance remain unsolved. In this review, we discuss aspects of niche establishment and integrity not yet fully understood and we compare it to the current knowledge in other model systems such as vertebrates and plants. We also address specific questions on stem cell maintenance and niche regulation in the Drosophila testis under the control of Hox genes. Finally, we provide insights on the striking functional conservation of homologous genes in plants and animals and their respective stem cell niches. Elucidating conserved mechanisms of stem cell control in both lineages could reveal the importance underlying this conservation and justify the evolutionary pressure to adapt homologous molecules for performing the same task.
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Affiliation(s)
- Fani Papagiannouli
- Centre for Organismal Studies (COS) Heidelberg and CellNetworks - Cluster of Excellence, Heidelberg, Germany.
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41
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Mohamed AAM, Kim Y. A target-specific feeding toxicity of β(1) integrin dsRNA against diamondback moth, Plutella xylostella. ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY 2011; 78:216-230. [PMID: 22105667 DOI: 10.1002/arch.20455] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Integrin is a cell-surface protein consisting of α and β heterodimers. A predicted amino acid sequence of an integrin subunit of the diamondback moth, Plutella xylostella, was highly homologous to other lepidopteran β1 subunits and possessed essential functional domains. The β1 integrin of P. xylostella (βPx1) was expressed in all developmental stages of P. xylostella. It was also expressed in all tested tissues including hemocyte, fat body, gut, and epidermis of last instar. When βPx1 expression was suppressed by injection of dsRNA specific to βPx1 (dsRNA(βPx1)), the treated larvae exhibited significant suppression in immune response and also suffered significant larval mortality. When dsRNA(βPx1) was orally fed to young larvae, it suppressed the expression of âPx1 and resulted in a significant mortality. By contrast, a dsRNA specific to β1 subunit of Spodoptera exigua gave little adverse effects on βPx1 expression and larval development when it was treated by injection or oral administration, though these two genes showed 71% sequence homology. These results suggest a target-specific RNA interference of dsRNA(βPx1), which causes significant mortality to P. xylostella by feeding treatment.
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Affiliation(s)
- Ahmed A M Mohamed
- Department of Bioresource Sciences, Andong National University, Andong, Korea
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Surakasi VP, Mohamed AAM, Kim Y. RNA interference of β1 integrin subunit impairs development and immune responses of the beet armyworm, Spodoptera exigua. JOURNAL OF INSECT PHYSIOLOGY 2011; 57:1537-1544. [PMID: 21856307 DOI: 10.1016/j.jinsphys.2011.08.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 08/04/2011] [Accepted: 08/04/2011] [Indexed: 05/31/2023]
Abstract
Integrin is a cell surface protein that is composed of α and β heterodimer and mediates cell interaction with extracellular matrix or other cells including microbial pathogens. A full length cDNA sequence (2862 bp) of a β1 subunit integrin (βSe1) was cloned from the beet armyworm, Spodoptera exigua. Phylogenetic analysis showed that βSe1 was clustered with other insect β integrin subunits with the highest amino acid sequence identity (98.3%) to β1 of Spodoptera litura. Structural analysis of the deduced amino acid sequence indicated that βSe1 possessed all functional domains known in other insect β1 integrins. RT-PCR analysis showed that βSe1 was expressed in all developmental stages and all tested tissues of S. exigua. Its expression was further upregulated in hemocytes by injections of various microbes from quantitative RT-PCR analysis. Injection of double-stranded βSe1 RNA (dsRNA(βSe1)) into late instar S. exigua suppressed βSe1 expression and resulted in significant reduction in pupal weight. The dsRNA(βSe1) injection significantly impaired hemocyte-spreading and nodule formation of S. exigua in response to bacterial challenge. Furthermore, oral ingestion of dsRNA(βSe1) induced reduction of βSe1 expression in midgut and resulted in significant mortality of S. exigua during immature development. These results suggest that βSe1 plays crucial roles in performing cellular immune responses as well as larval development in S. exigua.
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Affiliation(s)
- Venkata Prasad Surakasi
- Department of Bioresource Sciences, Andong National University, Andong 760-749, Republic of Korea
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Urbano JM, Domínguez-Giménez P, Estrada B, Martín-Bermudo MD. PS integrins and laminins: key regulators of cell migration during Drosophila embryogenesis. PLoS One 2011; 6:e23893. [PMID: 21949686 PMCID: PMC3174947 DOI: 10.1371/journal.pone.0023893] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2011] [Accepted: 07/27/2011] [Indexed: 01/16/2023] Open
Abstract
During embryonic development, there are numerous cases where organ or tissue formation depends upon the migration of primordial cells. In the Drosophila embryo, the visceral mesoderm (vm) acts as a substrate for the migration of several cell populations of epithelial origin, including the endoderm, the trachea and the salivary glands. These migratory processes require both integrins and laminins. The current model is that αPS1βPS (PS1) and/or αPS3βPS (PS3) integrins are required in migrating cells, whereas αPS2βPS (PS2) integrin is required in the vm, where it performs an as yet unidentified function. Here, we show that PS1 integrins are also required for the migration over the vm of cells of mesodermal origin, the caudal visceral mesoderm (CVM). These results support a model in which PS1 might have evolved to acquire the migratory function of integrins, irrespective of the origin of the tissue. This integrin function is highly specific and its specificity resides mainly in the extracellular domain. In addition, we have identified the Laminin α1,2 trimer, as the key extracellular matrix (ECM) component regulating CVM migration. Furthermore, we show that, as it is the case in vertebrates, integrins, and specifically PS2, contributes to CVM movement by participating in the correct assembly of the ECM that serves as tracks for migration.
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Affiliation(s)
- Jose M. Urbano
- Centro Andaluz de Biología del Desarrollo, (CSIC)-Universidad Pablo de Olavide, Sevilla, Spain
| | - Paloma Domínguez-Giménez
- Centro Andaluz de Biología Molecular y Medicina Regenerativa, (CSIC)-Universidad de Sevilla, Sevilla, Spain
| | - Beatriz Estrada
- Centro Andaluz de Biología del Desarrollo, (CSIC)-Universidad Pablo de Olavide, Sevilla, Spain
| | - María D. Martín-Bermudo
- Centro Andaluz de Biología del Desarrollo, (CSIC)-Universidad Pablo de Olavide, Sevilla, Spain
- * E-mail:
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Holmes RS, Rout UK. Comparative studies of vertebrate Beta integrin genes and proteins: ancient genes in vertebrate evolution. Biomolecules 2011; 1:3-31. [PMID: 24970121 PMCID: PMC4030831 DOI: 10.3390/biom1010003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2011] [Revised: 08/14/2011] [Accepted: 08/15/2011] [Indexed: 12/31/2022] Open
Abstract
Intregins are heterodimeric α- and β-subunit containing membrane receptor proteins which serve various cell adhesion roles in tissue repair, hemostasis, immune response, embryogenesis and metastasis. At least 18 α- (ITA or ITGA) and 8 β-integrin subunits (ITB or ITGB) are encoded on mammalian genomes. Comparative ITB amino acid sequences and protein structures and ITB gene locations were examined using data from several vertebrate genome projects. Vertebrate ITB genes usually contained 13-16 coding exons and encoded protein subunits with ~800 amino acids, whereas vertebrate ITB4 genes contained 36-39 coding exons and encoded larger proteins with ~1800 amino acids. The ITB sequences exhibited several conserved domains including signal peptide, extracellular β-integrin, β-tail domain and integrin β-cytoplasmic domains. Sequence alignments of the integrin β-cytoplasmic domains revealed highly conserved regions possibly for performing essential functions and its maintenance during vertebrate evolution. With the exception of the human ITB8 sequence, the other ITB sequences shared a predicted 19 residue α-helix for this region. Potential sites for regulating human ITB gene expression were identified which included CpG islands, transcription factor binding sites and microRNA binding sites within the 3'-UTR of human ITB genes. Phylogenetic analyses examined the relationships of vertebrate beta-integrin genes which were consistent with four major groups: 1: ITB1, ITB2, ITB7; 2: ITB3, ITB5, ITB6; 3: ITB4; and 4: ITB8 and a common evolutionary origin from an ancestral gene, prior to the appearance of fish during vertebrate evolution. The phylogenetic analyses revealed that ITB4 is the most likely primordial form of the vertebrate β integrin subunit encoding genes, that is the only β subunit expressed as a constituent of the sole integrin receptor 'α6β4' in the hemidesmosomes of unicellular organisms.
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Affiliation(s)
- Roger S Holmes
- School of Biomolecular and Physical Sciences, Griffith University, Nathan, 4111QLD, Australia.
| | - Ujjwal K Rout
- Department of Surgery, University of Mississippi Medical Center, Jackson, MS 38677, USA.
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Ozbek S, Balasubramanian PG, Chiquet-Ehrismann R, Tucker RP, Adams JC. The evolution of extracellular matrix. Mol Biol Cell 2011; 21:4300-5. [PMID: 21160071 PMCID: PMC3002383 DOI: 10.1091/mbc.e10-03-0251] [Citation(s) in RCA: 242] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
We present a perspective on the molecular evolution of the extracellular matrix (ECM) in metazoa that draws on research publications and data from sequenced genomes and expressed sequence tag libraries. ECM components do not function in isolation, and the biological ECM system or “adhesome” also depends on posttranslational processing enzymes, cell surface receptors, and extracellular proteases. We focus principally on the adhesome of internal tissues and discuss its origins at the dawn of the metazoa and the expansion of complexity that occurred in the chordate lineage. The analyses demonstrate very high conservation of a core adhesome that apparently evolved in a major wave of innovation in conjunction with the origin of metazoa. Integrin, CD36, and certain domains predate the metazoa, and some ECM-related proteins are identified in choanoflagellates as predicted sequences. Modern deuterostomes and vertebrates have many novelties and elaborations of ECM as a result of domain shuffling, domain innovations and gene family expansions. Knowledge of the evolution of metazoan ECM is important for understanding how it is built as a system, its roles in normal tissues and disease processes, and has relevance for tissue engineering, the development of artificial organs, and the goals of synthetic biology.
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Affiliation(s)
- Suat Ozbek
- Department of Molecular Evolution and Genomics, University of Heidelberg, D-69120 Heidelberg, Germany
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Hilario JD, Wang C, Beattie CE. Collagen XIXa1 is crucial for motor axon navigation at intermediate targets. Development 2010; 137:4261-9. [PMID: 21098567 DOI: 10.1242/dev.051730] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
During development, motor axons navigate from the spinal cord to their muscle targets in the periphery using stereotyped pathways. These pathways are broken down into shorter segments by intermediate targets where axon growth cones are believed to coordinate guidance cues. In zebrafish stumpy mutants, embryonic development proceeds normally; however, as trunk motor axons stall at their intermediate targets, suggesting that Stumpy is needed specifically for motor axon growth cones to proceed past intermediate targets. Fine mapping and positional cloning revealed that stumpy was the zebrafish homolog of the atypical FACIT collagen collagenXIXa1 (colXIX). colXIX expression was observed in a temporal and spatial pattern, consistent with a role in motor axon guidance at intermediate targets. Knocking down zebrafish ColXIX phenocopied the stumpy phenotype and this morpholino phenotype could be rescued by adding back either mouse or zebrafish colXIX RNA. The stumpy phenotype was also partially rescued in mutants by first knocking down zebrafish ColXIX and adding back colXIX RNA, suggesting that the mutation is acting as a dominant negative. Together, these results demonstrate a novel function for a FACIT collagen in guiding vertebrate motor axons through intermediate targets.
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Affiliation(s)
- Jona D Hilario
- The Ohio State University Center for Molecular Neurobiology and Department of Neuroscience, Columbus, OH 43210, USA
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Desiderio UV, Zhu X, Evans JP. ADAM2 interactions with mouse eggs and cell lines expressing α4/α9 (ITGA4/ITGA9) integrins: implications for integrin-based adhesion and fertilization. PLoS One 2010; 5:e13744. [PMID: 21060781 PMCID: PMC2966413 DOI: 10.1371/journal.pone.0013744] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2010] [Accepted: 10/06/2010] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Integrins are heterodimeric cell adhesion molecules, with 18 α (ITGA) and eight β (ITGB) subunits forming 24 heterodimers classified into five families. Certain integrins, especially the α(4)/α(9) (ITGA4/ITGA9) family, interact with members of the ADAM (a disintegrin and metalloprotease) family. ADAM2 is among the better characterized and also of interest because of its role in sperm function. Having shown that ITGA9 on mouse eggs participates in mouse sperm-egg interactions, we sought to characterize ITGA4/ITGA9-ADAM2 interactions. METHODOLOGY/PRINCIPAL FINDINGS An anti-β(1)/ITGB1 function-blocking antibody that reduces sperm-egg binding significantly inhibited ADAM2 binding to mouse eggs. Analysis of integrin subunit expression indicates that mouse eggs could express at least ten different integrins, five in the RGD-binding family, two in the laminin-binding family, two in the collagen-binding family, and ITGA9-ITGB1. Adhesion assays to characterize ADAM2 interactions with ITGA4/ITGA9 family members produced the surprising result that RPMI 8866 cell adhesion to ADAM2 was inhibited by an anti-ITGA9 antibody, noteworthy because ITGA9 has only been reported to dimerize with ITGB1, and RPMI 8866 cells lack detectable ITGB1. Antibody and siRNA studies demonstrate that ITGB7 is the β subunit contributing to RPMI 8866 adhesion to ADAM2. CONCLUSIONS/SIGNIFICANCE These data indicate that a novel integrin α-β combination, ITGA9-ITGB7 (α(9)β(7)), in RPMI 8866 cells functions as a binding partner for ADAM2. ITGA9 had previously only been reported to dimerize with ITGB1. Although ITGA9-ITGB7 is unlikely to be a widely expressed integrin and appears to be the result of "compensatory dimerization" occurring in the context of little/no ITGB1 expression, the data indicate that ITGA9-ITGB7 functions as an ADAM binding partner in certain cellular contexts, with implications for mammalian fertilization and integrin function.
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Affiliation(s)
- Ulyana V. Desiderio
- Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Xiaoling Zhu
- Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Janice P. Evans
- Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
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Mazza ME, Pang K, Reitzel AM, Martindale MQ, Finnerty JR. A conserved cluster of three PRD-class homeobox genes (homeobrain, rx and orthopedia) in the Cnidaria and Protostomia. EvoDevo 2010; 1:3. [PMID: 20849646 PMCID: PMC2938728 DOI: 10.1186/2041-9139-1-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Accepted: 07/05/2010] [Indexed: 01/25/2023] Open
Abstract
Background Homeobox genes are a superclass of transcription factors with diverse developmental regulatory functions, which are found in plants, fungi and animals. In animals, several Antennapedia (ANTP)-class homeobox genes reside in extremely ancient gene clusters (for example, the Hox, ParaHox, and NKL clusters) and the evolution of these clusters has been implicated in the morphological diversification of animal bodyplans. By contrast, similarly ancient gene clusters have not been reported among the other classes of homeobox genes (that is, the LIM, POU, PRD and SIX classes). Results Using a combination of in silico queries and phylogenetic analyses, we found that a cluster of three PRD-class homeobox genes (Homeobrain (hbn), Rax (rx) and Orthopedia (otp)) is present in cnidarians, insects and mollusks (a partial cluster comprising hbn and rx is present in the placozoan Trichoplax adhaerens). We failed to identify this 'HRO' cluster in deuterostomes; in fact, the Homeobrain gene appears to be missing from the chordate genomes we examined, although it is present in hemichordates and echinoderms. To illuminate the ancestral organization and function of this ancient cluster, we mapped the constituent genes against the assembled genome of a model cnidarian, the sea anemone Nematostella vectensis, and characterized their spatiotemporal expression using in situ hybridization. In N. vectensis, these genes reside in a span of 33 kb with the same gene order as previously reported in insects. Comparisons of genomic sequences and expressed sequence tags revealed the presence of alternative transcripts of Nv-otp and two highly unusual protein-coding polymorphisms in the terminal helix of the Nv-rx homeodomain. A population genetic survey revealed the Rx polymorphisms to be widespread in natural populations. During larval development, all three genes are expressed in the ectoderm, in non-overlapping territories along the oral-aboral axis, with distinct temporal expression. Conclusion We report the first evidence for a PRD-class homeobox cluster that appears to have been conserved since the time of the cnidarian-bilaterian ancestor, and possibly even earlier, given the presence of a partial cluster in the placozoan Trichoplax. Very similar clusters comprising these three genes exist in Nematostella and diverse protostomes. Interestingly, in chordates, one member of the ancestral cluster (homeobrain) has apparently been lost, and there is no linkage between rx and orthopedia in any of the vertebrates. In Nematostella, the spatial expression of these three genes along the body column is not colinear with their physical order in the cluster but the temporal expression is, therefore, using the terminology that has been applied to the Hox cluster genes, the HRO cluster would appear to exhibit temporal but not spatial colinearity. It remains to be seen whether the mechanisms responsible for the evolutionary conservation of the HRO cluster are the same mechanisms responsible for cohesion of the Hox cluster and other ANTP-class homeobox clusters that have been widely conserved throughout animal evolution.
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Affiliation(s)
- Maureen E Mazza
- Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA
| | - Kevin Pang
- Kewalo Marine Lab, Pacific Biosciences Research Center, University of Hawaii, 41 Ahui St., Honolulu, HI 96813, USA
| | - Adam M Reitzel
- Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.,Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA
| | - Mark Q Martindale
- Kewalo Marine Lab, Pacific Biosciences Research Center, University of Hawaii, 41 Ahui St., Honolulu, HI 96813, USA
| | - John R Finnerty
- Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA
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Sroka IC, Anderson TA, McDaniel KM, Nagle RB, Gretzer MB, Cress AE. The laminin binding integrin alpha6beta1 in prostate cancer perineural invasion. J Cell Physiol 2010; 224:283-8. [PMID: 20432448 DOI: 10.1002/jcp.22149] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Metastasizing prostate tumor cells invade along nerves innervating the encapsulated human prostate gland in a process known as perineural invasion. The extracellular matrix laminin class of proteins line the neural route and tumor cells escaping from the gland express the laminin binding integrin alpha6beta1 as a prominent cell surface receptor. Integrin alpha6beta1 promotes aggressive disease and supports prostate tumor cell metastasis to bone. Laminins and their integrin receptors are necessary for the development and maintenance of the peripheral nervous system, indicating the potential role for integrin receptors in directing prostate tumor cell invasion on nerves during perineural invasion.
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Affiliation(s)
- Isis C Sroka
- Department of Pharmacology, The University of Arizona, Tucson, Arizona, USA
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Redruello B, Louro B, Anjos L, Silva N, Greenwell RS, Canario AVM, Power DM. CRTAC1 homolog proteins are conserved from cyanobacteria to man and secreted by the teleost fish pituitary gland. Gene 2010; 456:1-14. [PMID: 20171266 DOI: 10.1016/j.gene.2010.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2009] [Revised: 02/02/2010] [Accepted: 02/05/2010] [Indexed: 12/01/2022]
Abstract
Cartilage acidic protein 1 (CRTAC1) gene expression is used as a marker for chondrocyte differentiation in stem cell-based tissue engineering. It is also transcribed outside the skeleton where at least two different transcripts are expressed in lung and brain. In the pituitary gland of the teleost fish sea bream Sparus auratus, we have found a transcript with a high degree of sequence identity to CRTAC1 family members but lacking the EGF-like calcium-binding domain encoding sequence of CRTAC1 and designated it as CRTAC2. Database searches revealed many previously unidentified members of the CRTAC1 and CRTAC2 in phylogenetically distant organisms, such as cyanobacteria, bryophyta, lancelets, and diverse representatives of vertebrates. Phylogenetic analyses showed that the genes encoding CRTAC1 and CRTAC2 proteins coexist in teleost fish genomes. Structural prediction analysis identified the N-terminal region of the CRTAC1/CRTAC2 family members as a potential seven-bladed beta-propeller structure, closely related to those of integrin alpha chains and glycosylphosphatidylinositol-specific phospholipase D1 protein families. This relationship is confirmed by phylogenetic analysis with the N-terminal domain of sea bream CRTAC2 as the most divergent sequence. Because teleost fishes are the only phylogenetic group where both CRTAC1 and CRTAC2 genes are present, they occupy a pivotal position in studies of the mechanisms governing the specific expression patterns of each gene/protein subfamily. This will be essential to elucidate their respective biological roles.
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Affiliation(s)
- Begoña Redruello
- Centre of Marine Sciences, University of Algarve, Gambelas, Faro, Portugal
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