{"doi":"10.7554/elife.87754","title":"β-Arrestin-dependent and -independent endosomal G protein activation by the vasopressin type 2 receptor","abstract":"The vasopressin type 2 receptor (V 2 R) is an essential G protein-coupled receptor (GPCR) in renal regulation of water homeostasis. Upon stimulation, the V 2 R activates Gα s and Gα q/11 , which is followed by robust recruitment of β-arrestins and receptor internalization into endosomes. Unlike canonical GPCR signaling, the β-arrestin association with the V 2 R does not terminate Gα s activation, and thus, Gα s -mediated signaling is sustained while the receptor is internalized. Here, we demonstrate that this V 2 R ability to co-interact with G protein/β-arrestin and promote endosomal G protein signaling is not restricted to Gα s , but also involves Gα q/11 . Furthermore, our data imply that β-arrestins potentiate Gα s /Gα q/11 activation at endosomes rather than terminating their signaling. Surprisingly, we found that the V 2 R internalizes and promote endosomal G protein activation independent of β-arrestins to a minor degree. These new observations challenge the current model of endosomal GPCR signaling and suggest that this event can occur in both β-arrestin-dependent and -independent manners.","journal":"eLife","year":2023,"id":349635,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1088319,"name":"Akim Abdul Guseinov","orcid":null,"position":1,"is_corresponding":false},{"id":986326,"name":"Hyunggu Hahn","orcid":"0000-0003-3532-7671","position":2,"is_corresponding":false},{"id":414345,"name":"Adam Wright","orcid":"0000-0001-6844-145X","position":3,"is_corresponding":false},{"id":308360,"name":"Irina G. Tikhonova","orcid":"0000-0002-6228-9431","position":4,"is_corresponding":false},{"id":348042,"name":"A. Thomsen","orcid":"0000-0003-1638-8911","position":5,"is_corresponding":false},{"id":348041,"name":"Bianca Plouffe","orcid":"0000-0002-8321-0796","position":6,"is_corresponding":false},{"id":965406,"name":"Carole Daly","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T01:12:19.059218Z","pmid":"37855711","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":[]}