{"doi":"10.1101/2021.10.09.463790","title":"Membrane phosphoinositides stabilize GPCR-arrestin complexes and provide temporal control of complex assembly and dynamics","abstract":"Summary Binding of arrestin to phosphorylated G protein-coupled receptors (GPCRs) is crucial for modulating signaling. Once internalized some GPCRs may complex with arrestin, while others interact transiently; this difference affects receptor signaling and recycling. Cell-based and in vitro biophysical assays reveal the role of membrane phosphoinositides (PIPs) in arrestin recruitment and GPCR-arrestin complex dynamics. We find that GPCRs broadly stratify into two groups, one requiring PIP-binding for arrestin recruitment and one that does not. Plasma membrane PIPs potentiate an active conformation of arrestin and stabilize GPCR-arrestin complexes by promoting a receptor core-engaged state of the complex. As allosteric modulators of GPCR-arrestin complex dynamics, membrane PIPs allow for additional conformational diversity beyond that imposed by GPCR phosphorylation alone. The dependance on membrane PIPs provides a mechanism for arrestin release from transiently associated GPCRs, allowing their rapid recycling, while explaining how stably associated GPCRs are able to engage G proteins at endosomes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216150,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":811567,"name":"Ryoji Kise","orcid":"0009-0000-6583-1719","position":1,"is_corresponding":false},{"id":227703,"name":"Benjamin Barsi‐Rhyne","orcid":"0000-0002-6610-1766","position":2,"is_corresponding":false},{"id":264644,"name":"Dirk H. Siepe","orcid":"0000-0002-0009-8023","position":3,"is_corresponding":false},{"id":251461,"name":"Franziska M. Heydenreich","orcid":"0000-0002-8049-4383","position":4,"is_corresponding":false},{"id":251459,"name":"Matthieu Masureel","orcid":"0000-0002-4059-6166","position":5,"is_corresponding":false},{"id":649556,"name":"Kouki Kawakami","orcid":"0000-0002-2507-8619","position":6,"is_corresponding":false},{"id":218189,"name":"K. Christopher García","orcid":"0000-0001-9273-0278","position":7,"is_corresponding":false},{"id":320027,"name":"Mark von Zastrow","orcid":"0000-0003-1375-6926","position":8,"is_corresponding":false},{"id":255551,"name":"Asuka Inoue","orcid":"0000-0003-0805-4049","position":9,"is_corresponding":false},{"id":251465,"name":"Brian K. Kobilka","orcid":"0000-0001-5958-3990","position":10,"is_corresponding":false},{"id":690841,"name":"John Janetzko","orcid":"0000-0003-1604-2515","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-18T23:53:00.192353Z","pmid":null,"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":[]}