The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity.

摘要: GPR56 is an adhesion G protein-coupled receptor that plays a key role in cortical development. Mutations to humans cause malformations of the cerebral cortex, but little known about normal function receptor. We found large N terminus (NT) cleaved from rest during processing remains non-covalently associated with seven-transmembrane region receptor, as indicated by coimmunoprecipitation two fragments both transfected cells and native tissue. also truncation NT results constitutive activation signaling, revealed increased GPR56-stimulated signaling upon transfection HEK-293 truncated GPR56, greatly enhanced binding β-arrestins relative full-length extensive ubiquitination cytotoxicity induced could be rescued cotransfection β-arrestin 2. Furthermore, we capable homophilic trans-trans interactions enhance activity. On basis these findings, suggest model which constrains activity N-terminal (GPR56 extracellular ligand and/or associations) can remove this inhibitory influence activate signaling.