CLN7 is an organellar chloride channel regulating lysosomal function.

ABSTRACT: Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive lysosomal storage diseases. One variant form of late-infantile NCL (vLINCL) is caused by mutations of a lysosomal membrane protein CLN7, the function of which has remained unknown. Here, we identified CLN7 as a novel endolysosomal chloride channel. Overexpression of CLN7 increases endolysosomal chloride currents and enlarges endolysosomes through a Ca²⁺/calmodulin-dependent way. Human CLN7 and its yeast homolog exhibit characteristics of chloride channels and are sensitive to chloride channel blockers. Moreover, CLN7 regulates lysosomal chloride conductance, luminal pH, and lysosomal membrane potential and promotes the release of lysosomal Ca²⁺ through transient receptor potential mucolipin 1 (TR

SUBMITTER: Wang Y 

PROVIDER: S-EPMC8673761 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature