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Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis

Official URL:https://doi.org/10.1126/science.1188070
PubMed:View item in PubMed
Creators Name:Novarino, G. and Weinert, S. and Rickheit, G. and Jentsch, T.J.
Journal Title:Science
Journal Abbreviation:Science
Page Range:1398-1401
Date:11 June 2010
Keywords:Adenosine Triphosphate, Chloride Channels, Chlorides, Electrophysiological Phenomena, Endocytosis, Endosomes, Hydrogen-Ion Concentration, Kidney Diseases, Proximal Kidney Tubules, Mutant Proteins, Proteinuria, Proton-Translocating ATPases, Protons, Animals, Mice
Abstract:Loss of the endosomal anion transport protein ClC-5 impairs renal endocytosis and underlies human Dent's disease. ClC-5 is thought to promote endocytosis by facilitating endosomal acidification through neutralization of proton pump currents. However, ClC-5 is a 2Cl(-)/H(+)-exchanger rather than a Cl(-) channel. We generated mice carrying the uncoupling E211A (unc) mutation that converts ClC-5 into a pure Cl(-) conductor. ATP-dependent acidification of renal endosomes was reduced in ClC-5 knockout mice, but normal in Clcn5(unc) mice. Surprisingly, however, their proximal tubular endocytosis was also impaired. Thus endosomal chloride concentration, which is raised by ClC-5 in exchange for protons accumulated by the H(+)-ATPase, may play a role in endocytosis.
Publisher:American Association for the Advancement of Science (U.S.A.)
Item Type:Article

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