Jan MöllerAli IsbilirTitiwat SungkawornBrendan OsbergChristos KarathanasisVikram SunkaraEugene O. GrushevskyiAndreas BockPaolo AnnibaleMike HeilemannChristof SchütteMartin J. LohseZuse Institute BerlinFreie Universität BerlinMax Delbruck Center for Molecular MedicineMahidol UniversityJulius-Maximilians-Universität WürzburgGoethe-Universität Frankfurt am MainISAR Bioscience GmbH2020-10-052020-10-052020-09-01Nature Chemical Biology. Vol.16, No.9 (2020), 946-95415524469155244502-s2.0-85089620365https://repository.li.mahidol.ac.th/handle/20.500.14594/58965© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. 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. [Figure not available: see fulltext.].Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/s41589-020-0566-1