The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms.

ABSTRACT: Adhesion G protein-coupled receptors (aGPCRs) are a large GPCR class that direct diverse fundamental biological processes. One prominent mechanism for aGPCR agonism involves autoproteolytic cleavage, which generates an activating, membrane-proximal tethered agonist (TA). How universal this mechanism is for all aGPCRs is unclear. Here, we investigate G protein induction principles of aGPCRs using mammalian latrophilin 3 (LPHN3) and cadherin EGF LAG-repeat 7-transmembrane receptors 1-3 (CELSR1-3), members of two aGPCR families conserved from invertebrates to vertebrates. LPHNs and CELSRs mediate fundamental aspects of brain development, yet CELSR signaling mechanisms are unknown. We find that CELSR1 and CELSR3 are cleavage deficient, while CELSR2 is efficiently cleaved. Despite differential

SUBMITTER: Bui DLH 

PROVIDER: S-EPMC10592476 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature