Fig. 10: Effects of MRAP2 at the MC4R.
From: MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor
The MC4R is activated by POMC-derived peptides from POMC-neurons the nucleus arcuatus, left side. In addition, AgRP/NPY neurons of the nucleus arcuatus produce AgRP which is in turn axonally transported to the PVN where the function of the MC4R is modulated by AgRP and POMC-derived peptides. Constitutively, the MC4R is in a higher oligomeric state at the plasma membrane of cells (square, left side). As such, it can interact with Gs and Gq as well as β-arrestin2, both constitutively as well as in response to POMC-derived molecules such as α-MSH and result in internalization. Upon co-expression of MRAP2 (square, right side), the equilibrium shifts in favor of monomers. Moreover, the interaction with MRAP2 favors Gs and Gq coupling, whereas ligand-dependent β-arrestin2 recruitment is impaired. These processes are further accompanied by a reduction in constitutive and ligand-dependent internalization.
