Orphan GPR61, GPR62 and GPR135 receptors and the melatonin MT₂ receptor reciprocally modulate their signaling functions.

ABSTRACT: Understanding the function of orphan G protein-coupled receptors (GPCRs), whose cognate ligand is unknown, is of major importance as GPCRs are privileged drug targets for many diseases. Recent phylogenetic studies classified three orphan receptors, GPR61, GPR62 and GPR135 among the melatonin receptor subfamily, but their capacity to bind melatonin and their biochemical functions are not well characterized yet. We show here that GPR61, GPR62 and GPR135 do not bind [³H]-melatonin nor 2-[¹²⁵I]iodomelatonin and do not respond to melatonin in several signaling assays. In contrast, the three receptors show extensive spontaneous ligand-independent activities on the cAMP, inositol phosphate and ß-arrestin pathways with distinct pathway-specific profiles. Spontaneous ß-arresti

SUBMITTER: Oishi A 

PROVIDER: S-EPMC5566548 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature