Proton-activated chloride channel PAC regulates endosomal acidification and transferrin receptor-mediated endocytosis.

ABSTRACT: During vesicular acidification, chloride (Cl^-), as the counterion, provides the electrical shunt for proton pumping by the vacuolar H⁺ ATPase. Intracellular CLC transporters mediate Cl^- influx to the endolysosomes through their 2Cl^-/H⁺ exchange activity. However, whole-endolysosomal patch-clamp recording also revealed a mysterious conductance releasing Cl^- from the lumen. It remains unknown whether CLCs or other Cl^- channels are responsible for this activity. Here, we show that the newly identified proton-activated Cl^- (PAC) channel traffics from the plasma membrane to endosomes via the classical YxxL motif. PAC deletion abolishes the endosomal Cl^- conductance, raises luminal Cl^- l

SUBMITTER: Osei-Owusu J 

PROVIDER: S-EPMC7869721 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature