| First Author | Novarino G | Year | 2010 |
| Journal | Science | Volume | 328 |
| Issue | 5984 | Pages | 1398-401 |
| PubMed ID | 20430975 | Mgi Jnum | J:160701 |
| Mgi Id | MGI:4454958 | Doi | 10.1126/science.1188070 |
| Citation | Novarino G, et al. (2010) Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science 328(5984):1398-401 |
| abstractText | 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. |
