Notch signaling from the endosome requires a conserved dileucine motif.

ABSTRACT: Notch signaling is reliant on γ-secretase-mediated processing, although the subcellular location where γ-secretase cleaves Notch to initiate signaling remains unresolved. Accumulating evidence demonstrates that Notch signaling is modulated by endocytosis and endosomal transport. In this study, we investigated the relationship between Notch transport itinerary and signaling capacity. In doing so, we discovered a highly conserved dileucine sorting signal encoded within the cytoplasmic tail that directs Notch to the limiting membrane of the lysosome for signaling. Mutating the dileucine motif led to receptor accumulation in cation-dependent mannose-phosphate receptor-positive tubular early endosomes and a reduction in Notch signaling capacity. Moreover, truncated receptor forms that mimic act

SUBMITTER: Zheng L 

PROVIDER: S-EPMC3564540 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature