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Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots

Item Type:Article
Title:Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots
Creators Name:Sungkaworn, T. and Jobin, M.L. and Burnecki, K. and Weron, A. and Lohse, M.J. and Calebiro, D.
Abstract:G-protein-coupled receptors mediate the biological effects of many hormones and neurotransmitters and are important pharmacological targets. They transmit their signals to the cell interior by interacting with G proteins. However, it is unclear how receptors and G proteins meet, interact and couple. Here we analyse the concerted motion of G-protein-coupled receptors and G proteins on the plasma membrane and provide a quantitative model that reveals the key factors that underlie the high spatiotemporal complexity of their interactions. Using two-colour, single-molecule imaging we visualize interactions between individual receptors and G proteins at the surface of living cells. Under basal conditions, receptors and G proteins form activity-dependent complexes that last for around one second. Agonists specifically regulate the kinetics of receptor-G protein interactions, mainly by increasing their association rate. We find hot spots on the plasma membrane, at least partially defined by the cytoskeleton and clathrin-coated pits, in which receptors and G proteins are confined and preferentially couple. Imaging with the nanobody Nb37 suggests that signalling by G-protein-coupled receptors occurs preferentially at these hot spots. These findings shed new light on the dynamic interactions that control G-protein-coupled receptor signalling.
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:550
Number:7677
Page Range:543-547
Date:26 October 2017
Official Publication:https://doi.org/10.1038/nature24264
PubMed:View item in PubMed

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