Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Trends Pharmacol Sci. 2018 Feb;39(2):96-108. doi: 10.1016/j.tips.2017.10.005. Epub 2017 Nov 6.
How G protein-coupled receptors (GPCRs) are organized at the cell surface remains highly contentious. Single-molecule (SM) imaging is starting to inform this debate as receptor behavior can now be visualized directly, without the need for interpreting ensemble data. The limited number of SM studies of GPCRs undertaken to date have strongly suggested that dimerization is at most transient, and that most receptors are monomeric at any given time. However, even SM data has its caveats and needs to be interpreted carefully. Here, we discuss the types of SM imaging strategies used to examine GPCR stoichiometry and consider some of these caveats. We also emphasize that attempts to resolve the debate ought to rely on orthogonal approaches to measuring receptor stoichiometry.
G 蛋白偶联受体 (GPCRs) 在细胞表面的组织方式仍然存在很大争议。单分子 (SM) 成像技术开始为这场争论提供信息，因为现在可以直接观察受体行为，而无需解释整体数据。迄今为止，对 GPCR 进行的少数几项 SM 研究强烈表明，二聚化最多是瞬时的，并且大多数受体在任何给定时间都是单体。然而，即使是 SM 数据也有其局限性，需要谨慎解释。在这里，我们讨论了用于检查 GPCR 数量的 SM 成像策略的类型，并考虑了其中的一些局限性。我们还强调，解决这场争论的尝试应该依赖于测量受体数量的正交方法。
