Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA.
FEBS J. 2021 Apr;288(8):2550-2561. doi: 10.1111/febs.15749. Epub 2021 Feb 22.
G protein-coupled receptors (GPCRs) canonically couple to specific Gα protein subtypes and β-arrestin adaptor proteins to initiate cellular signaling events. G protein-mediated signaling and β-arrestin-mediated signaling have broadly been considered separable. However, noncanonical interactions between G proteins and GPCRs are now appreciated that do not result in nucleotide exchange and classical G protein signaling. New findings also demonstrate direct interactions between G proteins and β-arrestins that are required for certain signaling and physiological events. Further adding to the intrigue of these newly appreciated G protein:β-arrestin complexes, only the Gαi subtype family members, and not Gαs, Gαq/11, or Gα12/13 subtypes, appear to form direct interactions with β-arrestin. Here, we review the recent discovery and initial characterization of G protein:β-arrestin complexes and describe how these complexes provide mechanistic insight into seemingly disparate observations. G protein:β-arrestin complexes build upon other observations of noncanonical G protein and β-arrestin signaling events to add an additional dimension to our understanding of GPCR signaling.
G 蛋白偶联受体（GPCRs）通常与特定的 Gα 蛋白亚型和β-arrestin 衔接蛋白偶联，从而启动细胞信号事件。G 蛋白介导的信号转导和β-arrestin 介导的信号转导通常被认为是可分离的。然而，现在已经认识到 G 蛋白和 GPCR 之间的非经典相互作用不会导致核苷酸交换和经典 G 蛋白信号转导。新的发现还表明，G 蛋白和β-arrestin 之间存在直接相互作用，这对于某些信号转导和生理事件是必需的。进一步增加了这些新出现的 G 蛋白：β-arrestin 复合物的复杂性，只有 Gαi 亚型家族成员，而不是 Gαs、Gαq/11 或 Gα12/13 亚型，似乎与β-arrestin 形成直接相互作用。在这里，我们回顾了 G 蛋白：β-arrestin 复合物的最新发现和初步特征，并描述了这些复合物如何为看似不同的观察结果提供机制见解。G 蛋白：β-arrestin 复合物建立在其他非经典 G 蛋白和β-arrestin 信号事件的观察基础上，为我们对 GPCR 信号转导的理解增加了一个额外的维度。
