Graduate School of Integrated Sciences for Life, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521, Japan.
Gen Comp Endocrinol. 2020 Jul 1;293:113474. doi: 10.1016/j.ygcen.2020.113474. Epub 2020 Mar 30.
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.
G 蛋白偶联受体（GPCRs）是最大的受体家族，约占当前药物靶点的 30%。然而，要充分阐明调节细胞内 GPCR 信号转导的机制却很困难。因此，有必要考虑并研究与内源性情况相关的 GPCR。我们的小组一直在研究参与体色（硬骨鱼和两栖动物）和摄食（脊椎动物）的 GPCR。在这里，我回顾了两个独立的 GPCR 系统（异源二聚体形成和初级纤毛 GPCR），它们可能成为 GPCR 研究的突破点。在硬骨鱼中，MCR 形成异源二聚体，这大大降低了它们对乙酰化配体的亲和力。在哺乳动物中，MCHR1 定位于纤毛膜中，并通过纤毛膜的独特信号缩短初级纤毛的长度。考虑到这两个新的 GPCR 概念有望促进对 GPCR 系统的整体认识。
