Amylin receptor subunit interactions are modulated by agonists and determine signaling.

ABSTRACT: Three amylin receptors (AMYRs) mediate the metabolic actions of the peptide hormone amylin and are drug targets for diabetes and obesity. AMY₁R, AMY₂R, and AMY₃R are heterodimers consisting of the G protein-coupled calcitonin receptor (CTR) paired with a RAMP1, -2, or -3 accessory subunit, respectively, which increases amylin potency. Little is known about AMYR subunit interactions and their role in signaling. Here, we show that the AMYRs have distinct basal subunit equilibriums that are modulated by peptide agonists and determine the cAMP signaling phenotype. Using a novel biochemical assay that resolves the AMYR heterodimers and free subunits, we found that the AMY_1/2R subunit equilibriums favored free CTR and RAMP1/2, and rat amylin and αCGRP

SUBMITTER: Gostynska SE 

PROVIDER: S-EPMC11482831 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature