De Oliveira, Paulo A.Moreno Guillén, EstefaníaCasajuana-Martin, NilCasadó Anguera, VerònicaCai, Ning-ShengCamacho-Hernandez, Gisela AndreaZhu, HuBonifazi, AlessandroHall, Matthew D.Weinshenker, DavidNewman, Amy HauckLogothetis, Diomedes E.Casadó, VicentPlant, Leigh D.Pardo, LeonardoFerré, Sergi2022-09-282022-09-282022-06-221043-6618https://hdl.handle.net/2445/189394Recent studies have proposed that heteromers of μ-opioid receptors (MORs) and galanin Gal1 receptors (Gal1Rs) localized in the mesencephalon mediate the dopaminergic effects of opioids. The present study reports converging evidence, using a peptide-interfering approach combined with biophysical and biochemical techniques, including total internal reflection fluorescence microscopy, for a predominant homodimeric structure of MOR and Gal1R when expressed individually, and for their preference to form functional heterotetramers when co-expressed. Results show that a heteromerization-dependent change in the Gal1R homodimeric interface leads to a switch in G-protein coupling from inhibitory Gi to stimulatory Gs proteins. The MOR-Gal1R heterotetramer, which is thus bound to Gs via the Gal1R homodimer and Gi via the MOR homodimer, provides the framework for a canonical Gs-Gi antagonist interaction at the adenylyl cyclase level. These novel results shed light on the intense debate about the oligomeric quaternary structure of G protein-coupled receptors, their predilection for heteromer formation, and the resulting functional significance.14 p.application/pdfengcc-by-nc-nd (c) De Oliveira, Paulo A. et al., 2022https://creativecommons.org/licenses/by-nc-nd/4.0/OligòmersProteïnes GOligomersG Proteinsinfo:eu-repo/semantics/article7239942022-09-28info:eu-repo/semantics/openAccess