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

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

Authors

  • Novarino G
  • Weinert S
  • Rickheit G
  • Jentsch TJ

Journal

Science (New York, N.Y.)

Publication Data

June 11, 2010

Associated Grants

None

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