Vacuolar H+-ATPase dysfunction rescues intralumenal vesicle cargo sorting in yeast lacking PI(3,5)P2 or Doa4.

ABSTRACT: Endosomes undergo a maturation process highlighted by a reduction in lumenal pH, a conversion of surface markers that prime endosome-lysosome fusion and the sequestration of ubiquitylated transmembrane protein cargos within intralumenal vesicles (ILVs). We investigated ILV cargo sorting in mutant strains of the budding yeast Saccharomyces cerevisiae that are deficient for either the lysosomal/vacuolar signaling lipid PI(3,5)P2 or the Doa4 ubiquitin hydrolase that deubiquitylates ILV cargos. Disruption of PI(3,5)P2 synthesis or Doa4 function causes a defect in sorting of a subset of ILV cargos. We show that these cargo-sorting defects are suppressed by mutations that disrupt Vph1, a subunit of vacuolar H+-ATPase (V-ATPase) complexes that acidify late endosomes and vacuoles. We further show

SUBMITTER: Wilson ZN 

PROVIDER: S-EPMC8353521 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature