Evolutionary plasticity in the requirement for force exerted by ligand endocytosis to activate C. elegans Notch proteins.

ABSTRACT: The conserved transmembrane receptor Notch has diverse and profound roles in controlling cell fate during animal development. In the absence of ligand, a negative regulatory region (NRR) in the Notch ectodomain adopts an autoinhibited confirmation, masking an ADAM protease cleavage site;^1,2 ligand binding induces cleavage of the NRR, leading to Notch ectodomain shedding as the first step of signal transduction.^3,4 In Drosophila and vertebrates, recruitment of transmembrane Delta/Serrate/LAG-2 (DSL) ligands by the endocytic adaptor Epsin, and their subsequent internalization by Clathrin-mediated endocytosis, exerts a "pulling force" on Notch that is essential to expose the cleavage site in the NRR.^4-6 Here, we show

SUBMITTER: Langridge PD 

PROVIDER: S-EPMC9133158 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature