单分子技术在G蛋白偶联受体二聚体中的应用  

Single-molecule methods in study of G protein-coupled receptor dimers

作　　者：蔡欣 王春勇 王德秀 苏文霞 鲁洪 王凤斌 CAI Xin;WANG Chun-yong;WANG De-xiu;SU Wen-xia;LU Hu;WANG Feng-bin(Clinical Medical school, Weifang Medical University,Weifang,Shandong 261053,China;Shouguang people's Hospital, Shouguang, Shandong 262700,China)

机构地区：[1]潍坊医学院临床医学院生理学教研室,山东潍坊261053 [2]寿光市人民医院肾内科,山东寿光262700

出　　处：《中国药理学通报》2019年第9期1206-1211,共6页Chinese Pharmacological Bulletin

基　　金：山东省自然科学基金资助项目(No ZR2018PC007);潍坊市科技发展计划项目(No 2018YX030)

摘　　要：G蛋白偶联受体(G protein-coupled receptors,GPCRs)不仅能以单体的形式发挥生物学作用,还可以相互作用形成同源/异源二聚体,后者是调节受体功能的一种重要方式,能改变下游信号蛋白的偶联,产生特异信号转导通路,介导一系列生理和病理过程,如心血管调节、能量代谢等。因此,GPCR二聚体成为新型药物靶点之一,备受关注。但是以往对GPCR二聚体的研究一直是按总体平均水平(ensemble average)进行,这隐藏了有价值的信息,失去了生物异质性的有用数据。单分子技术具有前所未有的时空分辨率,能够直接显示GPCR二聚体的内部状态、运动轨迹,以及随着时间和周围环境的变化而转变等,有助于进一步剖析GPCR二聚体的关键作用和相关药物的开发。因此,该文将对研究GPCR二聚体的单分子技术(如全内反射荧光显微镜、受激发射损耗显微技术、基态耗尽显微术等)进行简要综述。G-protein coupled receptors(GPCRs) can form biologically relevant dimers and oligomers, which are important to regulate receptor function. They have specific signal transduction pathways, thus mediating a series of physiological and pathological processes, such as cardiovascular regulation, energy metabolism, etc. GPCR dimers become one of the new drug targets, attracting increasing attention. Traditionally, the research on GPCR dimers have been performed on a population “ensemble average” level. However, the main problem is that there may be valuable information hidden in this “noise”. Single molecule technology has unprecedented spatial and temporal resolution, which can directly display the internal state, trajectory of GPCR dimers and the changes with time and surrounding environment. It helps to further analyze the key role and drug targets of GPCR dimers. Here, we review single-molecule techniques(such as total internal reflection fluorescence microscopy, stimulated emission loss microscopy and ground state depletion microscopy, etc.) that have been applied to GPCR dimers.

关 键 词：单分子技术 G蛋白偶联受体 二聚体 全内反射荧光显微镜 受激发射损耗显微技术 药物靶点 

分 类 号：R-05[医药卫生] R392.11