Drake Matthew T, Shenoy Sudha K, Lefkowitz Robert J
Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Circ Res. 2006 Sep 15;99(6):570-82. doi: 10.1161/01.RES.0000242563.47507.ce.
G protein-coupled receptors (GPCRs) play an integral role in the signal transduction of an enormous array of biological phenomena, thereby serving to modulate at a molecular level almost all components of human biology. This role is nowhere more evident than in cardiovascular biology, where GPCRs regulate such core measures of cardiovascular function as heart rate, contractility, and vascular tone. GPCR/ligand interaction initiates signal transduction cascades, and requires the presence of the receptor at the plasma membrane. Plasma membrane localization is in turn a function of the delivery of a receptor to and removal from the cell surface, a concept defined most broadly as receptor trafficking. This review illuminates our current view of GPCR trafficking, particularly within the cardiovascular system, as well as highlights the recent and provocative finding that components of the GPCR trafficking machinery can facilitate GPCR signaling independent of G protein activation.
G蛋白偶联受体(GPCRs)在大量生物现象的信号转导中发挥着不可或缺的作用,从而在分子水平上调节人体生物学的几乎所有组成部分。这一作用在心血管生物学中最为明显,GPCRs在其中调节心率、收缩力和血管张力等心血管功能的核心指标。GPCR/配体相互作用引发信号转导级联反应,并且需要受体存在于质膜上。质膜定位又是受体向细胞表面转运以及从细胞表面移除的结果,这一概念最广义地定义为受体转运。本综述阐明了我们目前对GPCR转运的看法,特别是在心血管系统中的看法,同时突出了最近一项引人关注的发现,即GPCR转运机制的组成部分可以在不依赖G蛋白激活的情况下促进GPCR信号传导。