Hot spots for GPCR signaling: lessons from single-molecule microscopy.

Autor: Calebiro D; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, UK; Institute of Pharmacology and Bio-Imaging Center, University of Würzburg, Germany. Electronic address: D.Calebiro@bham.ac.uk., Jobin ML; Institute of Pharmacology and Bio-Imaging Center, University of Würzburg, Germany.
Jazyk: angličtina
Zdroj: Current opinion in cell biology [Curr Opin Cell Biol] 2019 Apr; Vol. 57, pp. 57-63. Date of Electronic Publication: 2018 Dec 03.
DOI: 10.1016/j.ceb.2018.11.003
Abstrakt: G protein-coupled receptors (GPCRs) are among the best-studied membrane receptors, mainly due to their central role in human physiology, involvement in disease and relevance as drug targets. Although biochemical and pharmacological studies have characterized the main steps in GPCR signaling, how GPCRs produce highly specific responses in our cells remains insufficiently understood. New developments in single-molecule microscopy have made it possible to study the protein-protein interactions at the basis of GPCR signaling in previously inconceivable detail. Using this approach, it was recently possible to follow individual receptors and G proteins as they diffuse, interact and signal on the surface of living cells. This has revealed hot spots on the plasma membrane, where receptors and G proteins undergo transient interactions to produce rapid and local signals. Overall, these recent findings reveal a high degree of dynamicity and complexity in signaling by GPCRs, which provides a new basis to understand how these important receptors produce specific effects and might pave the way to innovative pharmacological approaches.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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