New perspectives on GPCRs: GPCR heterodimer formation (melanocortin receptor) and GPCR on primary cilia (melanin concentrating hormone receptor).

GPCRs are the largest family of receptors accounting for about 30% of the current drug targets. However, it is difficult to fully elucidate the mechanisms regulating intracellular GPCR signal regulation. It is thus important to consider and investigate GPCRs with respect to endogenous situations. Our group has been investigating GPCRs involved in body color (teleost and amphibian) and eating (vertebrate). Here, I review two independent GPCR systems (heterodimer formation and primary ciliated GPCR) that can be breakthroughs in GPCR research. In teleosts, MCRs form heterodimers, which significantly reduce their affinity for acetylated ligands. In mammals, MCHR1 is localized in the ciliary membrane and shortens the length of the primary cilia through a unique signal from the ciliary membrane. Considering these two new GPCR concepts is expected to advance the overall view of the GPCR system.