G protein coupled receptors (GPCRs) are among the most versatile receptors and constitute major drug targets representing 30 to 40% of drugs available on the market. About 100 GPCRs are orphans and have not been associated with an endogenous ligand, yet they have significant therapeutic potential. Among these orphan receptors, our laboratory sought to identify the function of GPR50, an orphan GPCR, sharing high sequence homology with other members of the melatonin receptor family. Human variants of GPR50 have been linked to neurological diseases such as bipolar disorder and major depressive disorder, but little data exists on this new receptor. We revealed its importance in leptin signaling (PMID: 22197240) and we recently demonstrated the protective role of GPR50 against breast cancer (PMID: 29572483). Our team has demonstrated various original regulatory mechanisms operated by GPR50 involving the regulation of the function of other receptors in common heterodimers (PMID: 16778767; PMID: 17077864; PMID: 29572483), or implicating the proteolytic cleavage of the large intracellular domain of GPR50 which migrates to the nucleus to directly regulate gene expression (PMID: 31900622).

Our objectives are to understand the pathophysiological importance of GPR50 and to search and develop new therapeutic drugs.

This project is carried out in collaboration with the teams of JS Silvestre / A Levoye (Inserm U970-PARCC), C Prunier (Saint-Antoine Inserm UMR_S 938), V Prévot (Inserm UMR-S 1172, Lille), J. Selent (GRIB, Barcelona).