Transport activity and presence of ClC‐7/Ostm1 complex account for different cellular functions. (12th May 2014)

• Record Type: Journal Article
• Authors: Weinert, Stefanie; Jabs, Sabrina; Hohensee, Svea; Chan, Wing Lee; Kornak, Uwe; Jentsch, Thomas J
• Is Part Of: EMBO reports. Volume 15:Number 7(2014:Jul.)
• Page Start: 784
• Page End: 791
• Publication Date: 2014-05-12
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201438553
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="main" id="embr201438553-abs-0001"> <title>Abstract</title> <p>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 <italic>Clcn7</italic>^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 <italic>Clcn7</italic>^td/td mice expressing an ion transport‐deficient mutant. Their osteopetrosis was as severe as in <italic>Clcn7</italic>^−/− mice, suggesting that the electric shunt provided by ClC‐7^unc can partially rescue osteoclast function. The normal coat colour of <italic>Clcn7</italic>^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 <italic>in vivo</italic> 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.</p> </abstract>