An in vivo screen identifies diverse domains that can act as force-dependent proteolytic switches for Notch activation.

ABSTRACT: Notch proteins are single-pass transmembrane receptors activated by sequential extracellular and intramembrane cleavages to release the cytosolic domains that function as transcription factors. Transmembrane ligands of the Delta/Serrate/LAG-2 (DSL) family activate Notch on neighboring cells by exerting a pulling force across the intercellular ligand-receptor bridge. This force is generated by Epsin-mediated endocytosis of the ligand into the signal-sending cell and results in the extracellular cleavage of the force-sensing negative regulatory region (NRR) of the receptor by an ADAM10 protease on the signal-receiving cell. Here, we used chimeric Notch and DSL proteins to screen for other domains that could function as ligand-dependent proteolytic switches in place of the NRR in the developi

SUBMITTER: Baker FC 

PROVIDER: S-EPMC12290919 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature