A summary and conclusions from the meeting.
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).
Marshall
Fiona H
FH
Department of Pharmacology, University of Cambridge, Cambridge CB2 1QJ, UK. fhm24@cam.ac.uk
D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction
D046911:Macromolecular Substances; D011956:Receptors, Cell Surface