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| Item Type: | Article |
|---|---|
| Title: | Chloride and the endosomal/lysosomal pathway: emerging roles of CLC chloride transporters |
| Creators Name: | Jentsch, T.J. |
| Abstract: | Several members of the CLC family of Cl--channels and aeuro'transporters are expressed in vesicles of the endocytotic / lysomomal pathway, all of which are acidified by V-type proton pumps. These CLC proteins are thought to facilitate vesicular acidification by neutralizing the electric current of the H+-ATPase. Indeed, the disruption of ClC-5 impaired the acidification of endosomes, and the knock-out of ClC-3 that of endosomes and synaptic vesicles. Knock-out (KO) mice are available for all vesicular CLCs (ClC-3 through ClC-7), and ClC-5 and ClC-7, as well as its I(2)-subunit Ostm1, are mutated in human disease. The associated mouse and human pathologies, ranging from impaired endocytosis and nephrolithiasis (ClC-5) to neurodegeneration (ClC-3), lysosomal storage disease (ClC-6, ClC-7/Ostm1) and osteopetrosis (ClC-7/Ostm1), were crucial in identifying the physiological roles of vesicular CLCs. Whereas the intracellular localization of ClC-6 and ClC 7/Ostm1 precluded biophysical studies, the partial expression of ClC-4 and 5 at the cell surface allowed the detection of strongly outwardly-rectifying currents that depended on anions and pH. Surprisingly, ClC-4 and ClC-5 (and probably ClC-3) do not function as Cl- channels, but rather as electrogenic Cl-/H+-exchangers. This hints at an important role for luminal chloride in the endosomal/lysosomal system. |
| Keywords: | Cl-channels, Endocytosis, Osteoclast, Animals, Mice |
| Source: | Journal of Physiology |
| ISSN: | 0022-3751 |
| Publisher: | Blackwell Publishing |
| Volume: | 578 |
| Number: | Pt 3 |
| Page Range: | 633-640 |
| Date: | February 2007 |
| Official Publication: | https://doi.org/10.1113/jphysiol.2006.124719 |
| PubMed: | View item in PubMed |
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