Single-molecule analysis reveals agonist-specific dimer formation of µ-opioid receptors

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Item Type:	Article
Title:	Single-molecule analysis reveals agonist-specific dimer formation of µ-opioid receptors
Creators Name:	Möller, J., Isbilir, A., Sungkaworn, T., Osberg, B., Karathanasis, C., Sunkara, V., Grushevskyi, E.O., Bock, A., Annibale, P., Heilemann, M., Schütte, C. and Lohse, M.J.
Abstract:	G-protein-coupled receptors (GPCRs) are key signaling proteins that mostly function as monomers, but for several receptors constitutive dimer formation has been described and in some cases is essential for function. Using single-molecule microscopy combined with super-resolution techniques on intact cells, we describe here a dynamic monomer-dimer equilibrium of µ-opioid receptors (µORs), where dimer formation is driven by specific agonists. The agonist DAMGO, but not morphine, induces dimer formation in a process that correlates both temporally and in its agonist- and phosphorylation-dependence with β-arrestin2 binding to the receptors. This dimerization is independent from, but may precede, µOR internalization. These data suggest a new level of GPCR regulation that links dimer formation to specific agonists and their downstream signals.
Keywords:	Ala(2)-MePhe(4)-Gly(5)-Enkephalin, beta-Arrestins, CHO Cells, Fluorescence Resonance Energy Transfer, Morphine, mu Opioid Receptors, Mutation, Naloxone, Naltrexone, Narcotic Antagonists, Phosphorylation, Protein Multimerization, Single Molecule Imaging, Animals, Cricetulus
Source:	Nature Chemical Biology
ISSN:	1552-4450
Publisher:	Nature Publishing Group
Volume:	16
Number:	9
Page Range:	946-954
Date:	September 2020
Official Publication:	https://doi.org/10.1038/s41589-020-0566-1
PubMed:	View item in PubMed

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