Marshall Fiona H
Department of Pharmacology, University of Cambridge, Cambridge CB2 1QJ, UK.
J Mol Neurosci. 2005;26(2-3):295-8. doi: 10.1385/JMN:26:2-3:295.
The Wenner-Gren meeting in Stockholm saw the arrival of a new era in the field of heptaspanning receptor oligomerization. The concept of direct physical and functionally relevant interactions between multiple seven transmembrane (7TMs) was considered by many to be an artifact of the experimental systems or techniques used for analysis. However, during the course of the meeting at Stockholm, we were presented with an overwhelming set of evidence ranging from actual photographs of receptor dimers, through biochemical and cellular evidence, up to physiologically relevant data in animal models and human cells. We agreed that the "hypothesis" of receptor oligomerization has come of age and can now essentially be considered an established "fact." Those of us submitting papers in the area no longer expect to get the same level of skepticism from referees (well, one can always hope!). The symposium began with an energizing talk from Lefkowitz, describing the early work in his lab leading to the cloning of the first 7TM the beta2AR, followed up with the many important discoveries on the mechanisms of receptor signaling and desensitization. We were brought right up to date on the current state of thinking on receptor signaling, much of which occurs not only through G proteins but through beta-arrestin and GRKs. The meeting was organized by those who laid the foundations of our current understanding of receptor-receptor interactions. As long ago as the early 1980s, Agnati and Fuxe demonstrated that receptor-receptor interactions occurred between neuropeptides and monoamine receptors in the CNS and proposed the idea of receptor mosaics made up of clusters of receptors (Agnati et al., 1982; Fuxe et al., 1983). During the 1990s, biochemical evidence suggesting dimerization of receptors was accumulating, particularly in the lab of one of the other meeting organizers, Michel Bouvier. Bouvier was the first to provide direct biochemical evidence for 7TM homodimers using coimmunoprecipitation of differentially tagged receptors (Hebert et al., 1996).
在斯德哥尔摩举行的文纳-格林会议见证了七跨膜受体寡聚化领域新时代的到来。许多人认为多个七跨膜（7TM）之间直接的物理和功能相关相互作用的概念是用于分析的实验系统或技术的人为产物。然而，在斯德哥尔摩会议期间，我们看到了一系列压倒性的证据，从受体二聚体的实际照片，到生化和细胞证据，再到动物模型和人类细胞中的生理相关数据。我们一致认为，受体寡聚化的“假说”已经成熟，现在基本上可以被视为既定的“事实”。我们这些在该领域提交论文的人不再期望从审稿人那里得到同样程度的怀疑态度（嗯，总还是可以抱有希望的！）。研讨会以莱夫科维茨充满活力的演讲拉开序幕，他讲述了自己实验室早期导致克隆首个7TM——β2肾上腺素能受体（β2AR）的工作，随后介绍了关于受体信号传导和脱敏机制的许多重要发现。我们了解到了受体信号传导当前的最新思考状态，其中很多不仅通过G蛋白发生，还通过β-抑制蛋白和G蛋白偶联受体激酶（GRK）发生。此次会议由那些奠定了我们目前对受体-受体相互作用理解基础的人组织。早在20世纪80年代初，阿尼亚蒂和富克斯就证明了中枢神经系统中神经肽和单胺受体之间存在受体-受体相互作用，并提出了由受体簇组成的受体镶嵌体的概念（阿尼亚蒂等人，1982年；富克斯等人，1983年）。在20世纪90年代，表明受体二聚化的生化证据不断积累，特别是在另一位会议组织者米歇尔·布维耶的实验室。布维耶是第一个使用差异标记受体的共免疫沉淀法为7TM同二聚体提供直接生化证据的人（赫伯特等人，1996年）。
