![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| Item Type: | Article |
|---|---|
| Title: | Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins |
| Creators Name: | Scheel, O., Zdebik, A.A., Lourdel, S. and Jentsch, T.J. |
| Abstract: | Eukaryotic members of the CLC gene family function as plasma membrane chloride channels, or may provide neutralizing anion currents for V-type H(+)-ATPases that acidify compartments of the endosomal/lysosomal pathway. Loss-of-function mutations in the endosomal protein ClC-5 impair renal endocytosis and lead to kidney stones, whereas loss of function of the endosomal/lysosomal protein ClC-7 entails osteopetrosis and lysosomal storage disease. Vesicular CLCs have been thought to be Cl- channels, in particular because ClC-4 and ClC-5 mediate plasma membrane Cl- currents upon heterologous expression. Here we show that these two mainly endosomal CLC proteins instead function as electrogenic Cl-/H+ exchangers (also called antiporters), resembling the transport activity of the bacterial protein ClC-e1, the crystal structure of which has already been determined. Neutralization of a critical glutamate residue not only abolished the steep voltage-dependence of transport, but also eliminated the coupling of anion flux to proton counter-transport. ClC-4 and ClC-5 may still compensate the charge accumulation by endosomal proton pumps, but are expected to couple directly vesicular pH gradients to Cl- gradients. |
| Keywords: | Antiporters, Bacterial Proteins, Cell Line, Chloride Channels, Chlorides, Electric Conductivity, Endosomes, Hydrogen-Ion Concentration, Ion Channel Gating, Ion Transport, Membrane Potentials, Missense Mutation, Oocytes, Patch-Clamp Techniques, Protons, Torpedo, Animals, Xenopus |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 436 |
| Number: | 7049 |
| Page Range: | 424-427 |
| Date: | 21 July 2005 |
| Official Publication: | https://doi.org/10.1038/nature03860 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
