Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal Cl^-/H⁺ Exchanger ClC-7.

ABSTRACT: ClC-7 is a ubiquitously expressed voltage-gated Cl^-/H⁺ exchanger that critically contributes to lysosomal ion homeostasis. Together with its β-subunit Ostm1, ClC-7 localizes to lysosomes and to the ruffled border of osteoclasts, where it supports the acidification of the resorption lacuna. Loss of ClC-7 or Ostm1 leads to osteopetrosis accompanied by accumulation of storage material in lysosomes and neurodegeneration. Interestingly, not all osteopetrosis-causing CLCN7 mutations from patients are associated with a loss of ion transport. Some rather result in an acceleration of voltage-dependent ClC-7 activation. Recently, a gain-of-function variant, ClC-7^Y715C, that yields larger ion currents upon heterologous expression, was identified in two patients

SUBMITTER: Bose S 

PROVIDER: S-EPMC10742274 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature