《生命科学》 2021, 33(1): 61-67
GPR50在肥胖及相关疾病中的作用研究进展
摘 要：
G蛋白偶联受体家族(GPCRs)是真核细胞膜表面最大的一类膜蛋白受体，能够被细胞外的多肽、糖类、脂类、离子、生物胺等激活，被认为参与了80%以上的细胞信号转导过程，是细胞信号转导中重要的蛋白质。GPCRs广泛参与生殖、发育、内分泌以及代谢等多种生理过程，同时与免疫性疾病、中枢神经系统疾病、糖尿病、心脏病、癌症等疾病的发生、发展密切相关。GPR50是GPCR的A家族成员，其氨基酸序列与褪黑素受体MT1和MT2有45%相同，目前仍是孤儿受体，其功能尚不明确，相关已发表的研究论文也不足百篇。任培根课题组近期的研究发现，孤儿受体GPR50在肥胖小鼠和正常小鼠的脂肪组织中表达差异显著，提示GPR50这一被认为主要在大脑中表达的GPCR在肥胖过程中可能具有潜在作用。该文将根据已有文献调研，从GPR50与褪黑素异二聚化、瘦素信号通路调节、脂质代谢调节等三方面阐述其在肥胖及相关疾病中的作用，为解析GPR50的生物学作用及其去孤儿化寻找思路。
通讯作者：任培根 , Email:peigen.ren@siat.ac.cn
Abstract:
G protein-coupled receptors (GPCRs) form the largest cell membrane receptor family responding to extracellular peptides, saccharides, lipids, ions and bioamines etc. GPCRs are involved in many physiological processes, including reproduction, evolution, endocrine, and metabolic processes, and are closely related to the development of immune diseases, central nervous system diseases, diabetes, heart diseases, cancers, and other diseases. GPR50 is an orphan receptor, a member of the GPCR A family. Its amino acid sequence is 45% identical to melatonin receptors MT1 and MT2. There are less than a hundred published studies about GPR50. Recently, our research group found that the orphan receptor GPR50 was expressed differentially in the adipose tissue between
obese and normal mice, suggesting that GPR50, a GPCR that is thought to be expressed mainly in the brain, may
have a potential role in fat metabolism. In this review, we discussed the role of GPR50 in obesity and related diseases from three aspects: heterodimerization of GPR50 with melatonin, regulation of leptin signaling pathway, and regulation of lipid metabolism, to find ideas for analyzing the biological role of GPR50 and its deorphanization.
Communication Author：REN Pei-Gen , Email:peigen.ren@siat.ac.cn
