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Title: | Preferential Gs protein coupling of the galanin Gal1 receptor in the μ-opioid-Gal1 receptor heterotetramer |
Author: | De Oliveira, Paulo A. Moreno Guillén, Estefanía Casajuana-Martin, Nil Casadó Anguera, Verònica Cai, Ning-Sheng Camacho-Hernandez, Gisela Andrea Zhu, Hu Bonifazi, Alessandro Hall, Matthew D. Weinshenker, David Newman, Amy Hauck Logothetis, Diomedes E. Casadó, Vicent Plant, Leigh D. Pardo, Leonardo Ferré, Sergi |
Keywords: | Oligòmers Proteïnes G Oligomers G Proteins |
Issue Date: | 22-Jun-2022 |
Publisher: | Elsevier B.V. |
Abstract: | Recent 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.phrs.2022.106322 |
It is part of: | Pharmacological Research, 2022, vol. 182, p. 106322 |
URI: | http://hdl.handle.net/2445/189394 |
Related resource: | https://doi.org/10.1016/j.phrs.2022.106322 |
ISSN: | 1043-6618 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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