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| Item Type: | Article |
|---|---|
| Title: | ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity |
| Creators Name: | Leisle, L. and Ludwig, C.F. and Wagner, F.A. and Jentsch, T.J. and Stauber, T. |
| Abstract: | Mutations in the ClC-7/Ostm1 ion transporter lead to osteopetrosis and lysosomal storage disease. Its lysosomal localization hitherto precluded detailed functional characterization. Using a mutated ClC-7 that reaches the plasma membrane, we now show that both the aminoterminus and transmembrane span of the Ostm1 β-subunit are required for ClC-7 Cl(-)/H(+)-exchange, whereas the Ostm1 transmembrane domain suffices for its ClC-7-dependent trafficking to lysosomes. ClC-7/Ostm1 currents were strongly outwardly rectifying owing to slow gating of ion exchange, which itself displays an intrinsically almost linear voltage dependence. Reversal potentials of tail currents revealed a 2Cl(-)/1H(+)-exchange stoichiometry. Several disease-causing CLCN7 mutations accelerated gating. Such mutations cluster to the second cytosolic cystathionine-β-synthase domain and potential contact sites at the transmembrane segment. Our work suggests that gating underlies the rectification of all endosomal/lysosomal CLCs and extends the concept of voltage gating beyond channels to ion exchangers. |
| Keywords: | Antiport, Chloride Channel, Conductance, Structure-Function, Trafficking |
| Source: | EMBO Journal |
| ISSN: | 0261-4189 |
| Publisher: | Nature Publishing Group |
| Volume: | 30 |
| Number: | 11 |
| Page Range: | 2140-2152 |
| Date: | 1 June 2011 |
| Official Publication: | https://doi.org/10.1038/emboj.2011.137 |
| PubMed: | View item in PubMed |
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