Melanocortin receptors form constitutive homo- and heterodimers

A significant number of G protein-coupled receptors are shown to form homo- or heterodimers/oligomers, and oligomerization of GPCRs may be a quite general phenomenon. We have here explored the possibility that the two closely related human melanocortin receptor 1 (MC1R) and melanocortin receptor 3 (MC3R) form dimers. Using bioluminescence resonance energy transfer (BRET2) we demonstrate that MC1 and MC3Rs form homo- and heterodimers, when expressed in Cos-7 cells. Treatment with agonist, partial agonist or antagonists did not modify the BRET2 signal for any of the receptor pairs studied, suggesting that the dimerization is not regulated by ligand binding. Rather our results indicate that melanocortin receptors exist as constitutively pre-formed dimers.