The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor.

ABSTRACT: Evidence indicates that endosomal entry promotes signaling by the Notch receptor, but the mechanisms involved are not clear. In a search for factors that regulate Notch activation in endosomes, we isolated mutants in Drosophila genes that encode subunits of the vacuolar ATPase (V-ATPase) proton pump. Cells lacking V-ATPase function display impaired acidification of the endosomal compartment and a correlated failure to degrade endocytic cargoes. V-ATPase mutant cells internalize Notch and accumulate it in the lysosome, but surprisingly also show a substantial loss of both physiological and ectopic Notch activation in endosomes. V-ATPase activity is required in signal-receiving cells for Notch signaling downstream of ligand activation but upstream of gamma-secretase-dependent S3 cleavage. Th

SUBMITTER: Vaccari T 

PROVIDER: S-EPMC2867318 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature