Distinct ClC-6 and ClC-7 Cl^- sensitivities provide insight into ClC-7's role in lysosomal Cl^- homeostasis.

ABSTRACT: ClC-6 and ClC-7 are closely related, intracellular Cl^- /H⁺ antiporters belonging to the CLC family of channels and transporters. They localize to acidic late endosomes and lysosomes and probably function in ionic homeostasis of these contiguous compartments. ClC-7 transport function requires association with the accessory protein Ostm1, whereas ClC-6 transport does not. To elucidate their roles in endo-lysosomes, we measured Cl^- - and pH-dependences of over-expressed wild-type ClC-6 and ClC-7, as well as disease-associated mutants, using high-resolution recording protocols. Lowering extracellular Cl^- (corresponding to luminal Cl^- in endo-lysosomes) reduced ClC-6 currents, whereas it increased transport activity of ClC-7/Ostm1. Low extr

SUBMITTER: Coppola MA 

PROVIDER: S-EPMC10842065 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature