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

@article{pmid35750299,

title = {Preferential Gs protein coupling of the galanin Gal_{1} receptor in the µ-opioid-Gal_{1} receptor heterotetramer},

author = {Paulo A De Oliveira and Estefanía Moreno and Nil Casajuana-Martin and Verònica Casadó-Anguera and Ning-Sheng Cai and Gisela Andrea Camacho-Hernandez and Hu Zhu and Alessandro Bonifazi and Matthew D Hall and David Weinshenker and Amy Hauck Newman and Diomedes E Logothetis and Vicent Casadó and Leigh D Plant and Leonardo Pardo and Sergi Ferré},

url = {https://pubmed.ncbi.nlm.nih.gov/35750299/},

doi = {10.1016/j.phrs.2022.106322},

issn = {1096-1186},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Pharmacol Res},

volume = {182},

pages = {106322},

abstract = {Recent studies have proposed that heteromers of µ-opioid receptors (MORs) and galanin Gal receptors (GalRs) 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 GalR when expressed individually, and for their preference to form functional heterotetramers when co-expressed. Results show that a heteromerization-dependent change in the GalR homodimeric interface leads to a switch in G-protein coupling from inhibitory Gi to stimulatory Gs proteins. The MOR-GalR heterotetramer, which is thus bound to Gs via the GalR 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}