G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and are of great interest as pharmacological targets. Although the occurrence of GPCR signaling nanodomains has long been hypothesized based on indirect evidence, this and other fundamental aspects of GPCR signaling have been difficult to prove. The advent of single-molecule microscopy methods, which allow direct visualization of individual membrane proteins with unprecedented spatiotemporal resolution, provides unique opportunities to address several of these open questions. Indeed, recent single-molecule studies have revealed that GPCRs and G proteins transiently interact with each other as well as with structural components of the plasma membrane, leading to the formation of dynamic complexes and ‘hot spots’ for GPCR signaling. Whereas we are only beginning to understand the implications of this unexpected level of complexity, single-molecule approaches are likely to play a crucial role to further dissect the protein–protein interactions that are at the heart of GPCR signaling.

G蛋白偶联受体（GPCR）构成了最大的膜受体家族，作为药理靶标引起了人们的极大兴趣。尽管长期以来一直基于间接证据来假设GPCR信号传导纳米域的发生，但是GPCR信号传导的这一方面和其他基本方面却难以证明。单分子显微镜方法的出现允许以前所未有的时空分辨率直接可视化单个膜蛋白，为解决这些未解决的问题提供了独特的机会。确实，最近的单分子研究表明，GPCR和G蛋白彼此之间以及与质膜的结构成分之间都进行了短暂的相互作用，从而导致了动态复合物的形成和GPCR信号传导的“热点”。