Cargando…

Functional coupling of V-ATPase and CLC-5

Dent’s disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl(-)/H(+) antiporter chloride channel 5 (CLC-5), which is ex...

Descripción completa

Detalles Bibliográficos
Autores principales: Satoh, Nobuhiko, Suzuki, Masashi, Nakamura, Motonobu, Suzuki, Atsushi, Horita, Shoko, Seki, George, Moriya, Kyoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215204/
https://www.ncbi.nlm.nih.gov/pubmed/28101447
http://dx.doi.org/10.5527/wjn.v6.i1.14
_version_ 1782491729931272192
author Satoh, Nobuhiko
Suzuki, Masashi
Nakamura, Motonobu
Suzuki, Atsushi
Horita, Shoko
Seki, George
Moriya, Kyoji
author_facet Satoh, Nobuhiko
Suzuki, Masashi
Nakamura, Motonobu
Suzuki, Atsushi
Horita, Shoko
Seki, George
Moriya, Kyoji
author_sort Satoh, Nobuhiko
collection PubMed
description Dent’s disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl(-)/H(+) antiporter chloride channel 5 (CLC-5), which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H(+)-ATPase (V-ATPase). Initially identified as a member of the CLC family of Cl(-) channels, CLC-5 was presumed to provide Cl(-) shunt into the endosomal lumen to dissipate H(+) accumulation by V-ATPase, thereby facilitating efficient endosomal acidification. However, recent findings showing that CLC-5 is in fact not a Cl(-) channel but a 2Cl(-)/H(+) antiporter challenged this classical shunt model, leading to a renewed and intense debate on its physiological roles. Cl(-) accumulation via CLC-5 is predicted to play a critical role in endocytosis, as illustrated in mice carrying an artificial Cl(-) channel mutation E211A that developed defective endocytosis but normal endosomal acidification. Conversely, a recent functional analysis of a newly identified disease-causing Cl(-) channel mutation E211Q in a patient with typical Dent’s disease confirmed the functional coupling between V-ATPase and CLC-5 in endosomal acidification, lending support to the classical shunt model. In this editorial, we will address the current recognition of the physiological role of CLC-5 with a specific focus on the functional coupling of V-ATPase and CLC-5.
format Online
Article
Text
id pubmed-5215204
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Baishideng Publishing Group Inc
record_format MEDLINE/PubMed
spelling pubmed-52152042017-01-19 Functional coupling of V-ATPase and CLC-5 Satoh, Nobuhiko Suzuki, Masashi Nakamura, Motonobu Suzuki, Atsushi Horita, Shoko Seki, George Moriya, Kyoji World J Nephrol Minireviews Dent’s disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl(-)/H(+) antiporter chloride channel 5 (CLC-5), which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H(+)-ATPase (V-ATPase). Initially identified as a member of the CLC family of Cl(-) channels, CLC-5 was presumed to provide Cl(-) shunt into the endosomal lumen to dissipate H(+) accumulation by V-ATPase, thereby facilitating efficient endosomal acidification. However, recent findings showing that CLC-5 is in fact not a Cl(-) channel but a 2Cl(-)/H(+) antiporter challenged this classical shunt model, leading to a renewed and intense debate on its physiological roles. Cl(-) accumulation via CLC-5 is predicted to play a critical role in endocytosis, as illustrated in mice carrying an artificial Cl(-) channel mutation E211A that developed defective endocytosis but normal endosomal acidification. Conversely, a recent functional analysis of a newly identified disease-causing Cl(-) channel mutation E211Q in a patient with typical Dent’s disease confirmed the functional coupling between V-ATPase and CLC-5 in endosomal acidification, lending support to the classical shunt model. In this editorial, we will address the current recognition of the physiological role of CLC-5 with a specific focus on the functional coupling of V-ATPase and CLC-5. Baishideng Publishing Group Inc 2017-01-06 2017-01-06 /pmc/articles/PMC5215204/ /pubmed/28101447 http://dx.doi.org/10.5527/wjn.v6.i1.14 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ 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.
spellingShingle Minireviews
Satoh, Nobuhiko
Suzuki, Masashi
Nakamura, Motonobu
Suzuki, Atsushi
Horita, Shoko
Seki, George
Moriya, Kyoji
Functional coupling of V-ATPase and CLC-5
title Functional coupling of V-ATPase and CLC-5
title_full Functional coupling of V-ATPase and CLC-5
title_fullStr Functional coupling of V-ATPase and CLC-5
title_full_unstemmed Functional coupling of V-ATPase and CLC-5
title_short Functional coupling of V-ATPase and CLC-5
title_sort functional coupling of v-atpase and clc-5
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215204/
https://www.ncbi.nlm.nih.gov/pubmed/28101447
http://dx.doi.org/10.5527/wjn.v6.i1.14
work_keys_str_mv AT satohnobuhiko functionalcouplingofvatpaseandclc5
AT suzukimasashi functionalcouplingofvatpaseandclc5
AT nakamuramotonobu functionalcouplingofvatpaseandclc5
AT suzukiatsushi functionalcouplingofvatpaseandclc5
AT horitashoko functionalcouplingofvatpaseandclc5
AT sekigeorge functionalcouplingofvatpaseandclc5
AT moriyakyoji functionalcouplingofvatpaseandclc5