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

• DOI: 10.1242/dev.045484
• Publication Date: 2010-05-11T11:47:15Z
• Authors: Thomas Vaccari; Serena Duchi; Katia Cortese; Carlo Tacchetti; David Bilder
• Keywords: V-ATPase

Evidence indicates that endosomal entry promotes signaling by the Notch receptor, but mechanisms involved are not clear. In a search for factors regulate activation in endosomes, we isolated mutants Drosophila genes encode subunits of vacuolar ATPase (V-ATPase) proton pump. Cells lacking V-ATPase function display impaired acidification compartment and correlated failure to degrade endocytic cargoes. mutant cells internalize accumulate it lysosome, surprisingly also show substantial loss both physiological ectopic endosomes. activity is required signal-receiving downstream ligand upstream gamma-secretase-dependent S3 cleavage. These data indicate V-ATPase, probably via early only degradation lysosome The results suggest ionic properties lumen might cleavage, providing rationale as well pathological control activity.