Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Feb 21, 2019; 10(2): 28-43
Published online Feb 21, 2019. doi: 10.4331/wjbc.v10.i2.28
Fasciculation and elongation zeta proteins 1 and 2: From structural flexibility to functional diversity
Mariana Bertini Teixeira, Marcos Rodrigo Alborghetti, Jörg Kobarg
Mariana Bertini Teixeira, Jörg Kobarg, Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas, Campinas 13083-862, Brazil
Marcos Rodrigo Alborghetti, Department of Cell Biology, University of Brasilia, Brasilia 70919-970, Brazil
Jörg Kobarg, Faculty of Pharmaceutical Sciences, University of Campinas, Campinas 13083-862, Brazil
Author contributions: Teixeira MB, Alborghetti MR and Kobarg J performed the literature search, analyses and interpretation of the data; elaborated the figures; conceived the overall idea of the review, elaborated the final version of the text together; all the authors read, revised and approved the final version.
Conflict-of-interest statement: The authors declare no conflict-of-interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jörg Kobarg, PhD, Full Professor, Molecular Biologist, Faculty of Pharmaceutical Sciences, University of Campinas, Rua Monteiro Lobato 255, Bloco F, Sala 03, Campinas 13083-862, Brazil. jorgkoba@unicamp.br
Telephone: +55-19-35211443
Received: November 29, 2018
Peer-review started: November 29, 2018
First decision: December 24, 2018
Revised: January 2, 2019
Accepted: January 28, 2019
Article in press: January 28, 2019
Published online: February 21, 2019
Abstract

Fasciculation and elongation zeta/zygin (FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve slowly and in general have intrinsically disordered regions. In 1985, unc-76 gene was firstly described and involved in axonal growth in C. elegans, and in 1997 Bloom and Horvitz enrolled also the human homologues genes, FEZ1 and FEZ2, in this process. While nematodes possess one gene (unc-76), mammalians have one more copy (FEZ1 and FEZ2). Several animal models have been used to study FEZ family functions like: C. elegans, D. melanogaster, R. novergicus and human cells. Complementation assays were performed and demonstrated the function conservation between paralogues. Human FEZ1 protein is more studied followed by UNC-76 and FEZ2 proteins, respectively. While FEZ1 and UNC-76 shared interaction partners, FEZ2 evolved and increased the number of protein-protein interactions (PPI) with cytoplasmatic partners. FEZ proteins are implicated in intracellular transport, acting as bivalent cargo transport adaptors in kinesin-mediated movement. Especially in light of this cellular function, this family of proteins has been involved in several processes like neuronal development, neurological disorders, viral infection and autophagy. However, nuclear functions of FEZ proteins have been explored as well, due to high content of PPI with nuclear proteins, correlating FEZ1 expression to Sox2 and Hoxb4 gene regulation and retinoic acid signaling. These recent findings open new avenue to study FEZ proteins functions and its involvement in already described processes. This review intends to reunite aspects of evolution, structure, interaction partners and function of FEZ proteins and correlate them to physiological and pathological processes.

Keywords: Hub, Intrinsically disordered, FEZ, Protein-protein interaction, Neuronal development, Retinoic acid signaling, Interactomics

Core tip: Fasciculation and elongation zeta/zygin (FEZ) proteins are intrinsically disordered and hub proteins involved in many cellular functions, acting as a bivalent adaptor of kinesin-based movement. These proteins are associated to several processes like neuronal development, neurological disorders, viral infection and autophagy. However, novel nuclear functions are being described, shedding more light to their role. This review intends to reunite aspects of evolution, structure, interaction partners and function of FEZ proteins and correlate them to physiological and pathological processes.