Common gating of both CLC subunits underlies voltage-dependent activation of the 2Cl-/1H+-exchanger ClC-7/Ostm1
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منابع مشابه
ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity.
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 transmembra...
متن کاملA missense mutation accelerating the gating of the lysosomal Cl−/H+-exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle
Chloride-proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either protein have been found to underlie osteopetrosis in mice and humans. Some human disease-causing CLCN7 mutations accelerate the usually slow voltage-dep...
متن کاملVoltage-dependent charge movement associated with activation of the CLC-5 2Cl−/1H+ exchanger
The family of CLC proteins comprises both Cl(-) channels and Cl(-)/H(+) exchange transporters with varying degrees of voltage dependence. The human CLC-5 is an electrogenic voltage-dependent 2Cl(-)/1H(+) exchanger that gives rise to strongly outwardly rectifying currents when expressed. We conducted whole-cell recordings from HEK293 cells transiently transfected with either wild-type CLC-5 or a...
متن کاملTransport activity and presence of ClC-7/Ostm1 complex account for different cellular functions.
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 generat...
متن کاملScientific Report Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions
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 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 mice exp...
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تاریخ انتشار 2016