Large transient capacitive currents in wild-type lysosomal Cl-/H+ antiporter ClC-7 and residual transport activity in the proton glutamate mutant E312A.

ABSTRACT: ClC-7 is a lysosomal 2 Cl-/1 H+ antiporter of the CLC protein family, which comprises Cl- channels and other Cl-/H+ antiporters. Mutations in ClC-7 and its associated β subunit Ostm1 lead to osteopetrosis and lysosomal storage disease in humans and mice. Previous studies on other mammalian CLC transporters showed that mutations of a conserved, intracellularly located glutamate residue, the so-called proton glutamate, abolish steady-state transport activity but increase transient capacitive currents associated with partial reactions of the transport cycle. In contrast, we observed large, transient capacitive currents for the wild-type ClC-7, which depend on external pH and internal, but not external, Cl-. Very similar transient currents were observed for the E312A mutant of the proton gluta

SUBMITTER: Pusch M 

PROVIDER: S-EPMC7681918 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature