DS0411 -

Novel functions for orphan G protein-coupled receptors – the GPR50/TGFß receptor complex – Tbeta-ORPH

Submission summary

Seven transmembrane (7TM) domain G protein-coupled receptors are among the most versatile and evolutionary successful protein families and constitute major drug targets. Out of the 400 non-odorant members identified in humans, approximately 100 remain orphans that have not been matched with an endogenous ligand. Apart from the classical deorphanization strategies, several alternative strategies provide new insights into the function of these proteins, which have great therapeutic potential. Indeed, we proposed a new concept to define the function of orphan GPCRs that does not rely on their putative capacity to respond to a ligand but rather on their capacity to allosterically regulate the function of other receptors in common protein complexes. Among the orphan GPCRs, GPR50 attracted particular interest due to its involvement in metabolic and mental disorders and its capacity to modulate the function of other receptors. The present project aims to decipher ligand-independent functions of GPR50 in several pathophysiological systems. Expending the function of orphan 7TM proteins like GPR50 beyond their potential ligand-dependent functions opens new conceptual and therapeutic avenues for these unexplored drug targets.

Project coordination

Julie DAM (Equipe Pharmacologie fonctionnelle et Physiopathologie des récepteurs membranaires, Institut Cochin)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


UMRS 970 Paris Centre de recherche Cardiovasculaire
UPD Equipe Pharmacologie fonctionnelle et Physiopathologie des récepteurs membranaires, Institut Cochin
CRSA Institut national de la santé et de la recherche médicale

Help of the ANR 437,000 euros
Beginning and duration of the scientific project: September 2016 - 36 Months

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