{"doi":"10.1016/j.phrs.2022.106322","title":"Preferential Gs protein coupling of the galanin Gal1 receptor in the µ-opioid-Gal1 receptor heterotetramer","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.","journal":"Pharmacological Research","year":2022,"id":247026,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290972,"name":"Estefanía Moreno","orcid":"0000-0002-2491-5753","position":1,"is_corresponding":false},{"id":884388,"name":"Nil Casajuana-Martín","orcid":"0000-0002-9007-274X","position":2,"is_corresponding":false},{"id":290979,"name":"Verònica Casadó-Anguera","orcid":"0000-0001-8532-2954","position":3,"is_corresponding":false},{"id":290973,"name":"Ning-Sheng Cai","orcid":"0000-0002-7749-5131","position":4,"is_corresponding":false},{"id":372199,"name":"Gisela Andrea Camacho‐Hernandez","orcid":"0000-0002-1533-093X","position":5,"is_corresponding":false},{"id":257078,"name":"Hu Zhu","orcid":null,"position":6,"is_corresponding":false},{"id":417317,"name":"Alessandro Bonifazi","orcid":"0000-0002-7306-0114","position":7,"is_corresponding":false},{"id":255126,"name":"Matthew D. Hall","orcid":"0000-0002-5073-442X","position":8,"is_corresponding":false},{"id":317261,"name":"David Weinshenker","orcid":"0000-0002-3678-6215","position":9,"is_corresponding":false},{"id":348848,"name":"Amy Hauck Newman","orcid":"0000-0001-9065-4072","position":10,"is_corresponding":false},{"id":659779,"name":"Diomedes E. Logothetis","orcid":"0000-0002-0576-884X","position":11,"is_corresponding":false},{"id":290983,"name":"Vicent Casadó","orcid":"0000-0002-1764-3825","position":12,"is_corresponding":false},{"id":325170,"name":"Leigh D. Plant","orcid":"0000-0002-1622-1655","position":13,"is_corresponding":false},{"id":270720,"name":"Leonardo Pardo","orcid":"0000-0003-1778-7420","position":14,"is_corresponding":false},{"id":290984,"name":"Sergi Ferré","orcid":"0000-0002-1747-1779","position":15,"is_corresponding":false},{"id":884387,"name":"Paulo Alexandre de Oliveira","orcid":"0000-0002-0852-4920","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:23:53.369530Z","pmid":"35750299","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}