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 calcitonin receptor (CTR), a G protein-coupled receptor, paired with a RAMP1, RAMP2, or RAMP3 accessory subunit, respectively, which increases amylin potency. Here, we found that the AMYRs had distinct basal subunit equilibria that were modulated by peptide agonists and determined the extent of cAMP signaling downstream of receptor activation. By developing a biochemical assay that resolves the AMYR heterodimers and free subunits, we found that the AMY₁R and AMY₂R subunit distributions favored free CTR and RAMPs and that rat amylin promoted a

SUBMITTER: Gostynska SE 

PROVIDER: S-EPMC12410446 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature