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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Functional coupling of V-ATPase and CLC-5
Nobuhiko Satoh, Masashi Suzuki, Motonobu Nakamura, Atsushi Suzuki, Shoko Horita, Department of Internal Medicine, Faculty of Medicine, the University of Tokyo Hospital, Tokyo 113-8655, Japan
George Seki, Department of Endocrinology and Nephrology, Yaizu City Hospital, Shizuoka 425-8505, Japan
Kyoji Moriya, Department of Infection Control and Prevention, the University of Tokyo Hospital, Tokyo 113-8655, Japan
Author contributions: All authors contributed to this paper.
Conflict-of-interest statement: The authors declare no conflict of interest related to this publication.
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/
Correspondence to: Nobuhiko Satoh, MD, Department of Internal Medicine, Faculty of Medicine, the University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. nosatou-tky@umin.ac.jp
Telephone: +81-3-38155411 Fax: +81-3-58008806
Received: August 12, 2016
Peer-review started: August 12, 2016
First decision: September 30, 2016
Revised: October 12, 2016
Accepted: November 1, 2016
Article in press: November 2, 2016
Published online: January 6, 2017
Peer-review started: August 12, 2016
First decision: September 30, 2016
Revised: October 12, 2016
Accepted: November 1, 2016
Article in press: November 2, 2016
Published online: January 6, 2017
Core Tip
Core tip: Chloride channel 5 (CLC-5) mutations cause Dent’s disease, which is characterized by renal proximal tubulopathy due to defective endocytosis. Recent revelations that CLC-5 is a 2Cl-/H+ antiporter and not a Cl- channel challenged the classical model proposing CLC-5 as a Cl- shunt to facilitate V-ATPase-mediated endosomal acidification. Therefore, physiological roles of CLC-5 and its interaction with V-ATPase in endosomal acidification and/or endocytosis are intensely debated. Recent functional analysis of a novel pure Cl- channel mutant from a Dent’s disease patient indicated a possible functional coupling between V-ATPase and CLC-5 not only in endosomal acidification but also at the plasma membrane.