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| Item Type: | Article |
|---|---|
| Title: | Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions |
| Creators Name: | Weinert, S. and Jabs, S. and Hohensee, S. and Chan, W.L. and Kornak, U. and Jentsch, T.J. |
| Abstract: | Loss of the lysosomal ClC-7/Ostm1 2Cl(-)/H(+) exchanger causes lysosomal storage disease and osteopetrosis in humans and additionally changes fur colour in mice. Its conversion into a Cl(-) conductance in Clcn7(unc/unc) mice entails similarly severe lysosomal storage, but less severe osteopetrosis and no change in fur colour. To elucidate the basis for these phenotypical differences, we generated Clcn7(td/td) mice expressing an ion transport-deficient mutant. Their osteopetrosis was as severe as in Clcn7(-/-) mice, suggesting that the electric shunt provided by ClC-7(unc) can partially rescue osteoclast function. The normal coat colour of Clcn7(td/td) mice and their less severe neurodegeneration suggested that the ClC-7 protein, even when lacking measurable ion transport activity, is sufficient for hair pigmentation and that the conductance of ClC-7(unc) is harmful for neurons. Our in vivo structure-function analysis of ClC-7 reveals that both protein-protein interactions and ion transport must be considered in the pathogenesis of ClC-7-related diseases. |
| Keywords: | Acidification, Anion Transport, Grey-Lethal, Lysosome, Wnt Signalling, Animals, Mice |
| Source: | EMBO Reports |
| ISSN: | 1469-221X |
| Publisher: | EMBO Press / Wiley |
| Volume: | 15 |
| Number: | 7 |
| Page Range: | 784-791 |
| Date: | 1 July 2014 |
| Official Publication: | https://doi.org/10.15252/embr.201438553 |
| PubMed: | View item in PubMed |
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