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.
Pubmed ID: 20430975 RIS Download
Mesh terms: Adenosine Triphosphate | Animals | Chloride Channels | Chlorides | Electrophysiological Phenomena | Endocytosis | Endosomes | Hydrogen-Ion Concentration | Kidney Diseases | Kidney Tubules, Proximal | Mice | Mice, Knockout | Mutant Proteins | Proteinuria | Proton-Translocating ATPases | Protons
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