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Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions

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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., Jabs, S., Hohensee, S., Chan, W.L., 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
Publisher:EMBO Press / Wiley
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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