Evidence for Protein–Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143

Protein-protein interactions between G protein-coupled receptors (GPCRs) can augment their functionality and increase the repertoire of signaling pathways they regulate. New therapeutics designed to modulate such may allow for targeting a specific GPCR activity, thus reducing potential side effects. Dopamine receptor (DR) heteromers are promising candidates targeted therapy neurological conditions as Parkinson’s disease since current treatments have severe To facilitate development therapies, it is necessary identify various DR binding partners. We report here new interaction partner DRD2 DRD3, orphan 143 (GPR143), an atypical that plays multiple roles in pigment cells expressed several regions brain. previously demonstrated DRD2/ DRD3 antagonist pimozide also modulates GPR143 activity. Using confocal microscopy two FRET methods, we observed DRs colocalize interact at intracellular membranes. Furthermore, co-expression wildtype resulted 57% 67% decrease respectively, determined by ?-Arrestin recruitment assay. GPR143-DR dimerization negatively activity changing affinity dopamine or delaying delivery plasma membrane.