Preferential Gs protein coupling of the galanin Gal1 receptor in the μ-opioid-Gal1 receptor heterotetramer

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...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/189394
Acceso en línea:https://hdl.handle.net/2445/189394
Access Level:acceso abierto
Palabra clave:Oligòmers
Proteïnes G
Oligomers
G Proteins
Descripción
Sumario: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.

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