| First Author | Weinert S | Year | 2014 |
| Journal | EMBO Rep | Volume | 15 |
| Issue | 7 | Pages | 784-91 |
| PubMed ID | 24820037 | Mgi Jnum | J:217031 |
| Mgi Id | MGI:5612937 | Doi | 10.15252/embr.201438553 |
| Citation | Weinert S, et al. (2014) Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions. EMBO Rep 15(7):784-91 |
| abstractText | 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. |
