Referenced in: none

Automatically associated channels: ClC4 , ClC5

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

Authors: Gaia Novarino, Stefanie Weinert, Gesa Rickheit, Thomas J Jentsch

Journal, date & volume: Science, 2010 Jun 11 , 328, 1398-401

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20430975

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 the neutralization of proton pump currents. However, ClC-5 is a 2 chloride (Cl-)/proton (H+) exchanger rather than a Cl- channel. We generated mice that carry the uncoupling E211A (unc) mutation that converts ClC-5 into a pure Cl- conductor. Adenosine triphosphate (ATP)-dependent acidification of renal endosomes was reduced in mice in which ClC-5 was knocked out, but normal in Clcn5(unc) mice. 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.