• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization.

One-third of the approximately 400 nonodorant G protein-coupled receptors (GPCRs) are still orphans. Although a considerable number of these receptors are likely to transduce cellular signals in response to ligands that remain to be identified, they may also have ligand-independent functions. Several members of the GPCR family have been shown to modulate the function of other receptors through heterodimerization. We show that GPR50, an orphan GPCR, heterodimerizes constitutively and specifically with MT(1) and MT(2) melatonin receptors, using biochemical and biophysical approaches in intact cells. Whereas the association between GPR50 and MT(2) did not modify MT(2) function, GPR50 abolished high-affinity agonist binding and G protein coupling to the MT(1) protomer engaged in the heterodimer. Deletion of the large C-terminal tail of GPR50 suppressed the inhibitory effect of GPR50 on MT(1) without affecting heterodimerization, indicating that this domain regulates the interaction of regulatory proteins to MT(1). Pairing orphan GPCRs to potential heterodimerization partners might be of clinical importance and may become a general strategy to better understand the function of orphan GPCRs.

Pubmed ID: 16778767


  • Levoye A
  • Dam J
  • Ayoub MA
  • Guillaume JL
  • Couturier C
  • Delagrange P
  • Jockers R


The EMBO journal

Publication Data

July 12, 2006

Associated Grants


Mesh Terms

  • Arrestins
  • Cell Line
  • Dimerization
  • Down-Regulation
  • Humans
  • Ligands
  • Melatonin
  • Mutation
  • Nerve Tissue Proteins
  • Protein Binding
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • Signal Transduction