{"doi":"10.1073/pnas.2011023118","title":"β-arrestin–dependent PI(4,5)P <sub>2</sub> synthesis boosts GPCR endocytosis","abstract":"Significance Stimulation of protease-activated receptor 2 (PAR2) at the plasma membrane triggers a branching cascade of interrelated events in several cellular compartments. In one branch, the G protein G q couples to phospholipase C, and the membrane phosphoinositide lipids PI(4,5)P 2 and PI(4)P are depleted. In another branch, the receptor becomes desensitized by becoming phosphorylated, bound to β-arrestin, and internalized by clathrin-coated pits. This second branch needs PI(4,5)P 2 at several steps. We found that β-arrestin in complex with receptors stably binds to clathrin-coated pits and increases transient binding of the PI(4,5)P 2 synthetic enzyme PIP5K-Iγ. Then, this complex in clathrin-coated pits boosts the rate of PI(4,5)P 2 synthesis from Golgi and plasma membrane PI(4)P, so that PI(4,5)P 2 becomes elevated. The new PI(4,5)P 2 allows receptor internalization.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":180240,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"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":483358,"name":"Yifei Jiang","orcid":"0000-0003-1818-4541","position":1,"is_corresponding":false},{"id":267917,"name":"Jong Bae Seo","orcid":"0000-0001-5058-5156","position":2,"is_corresponding":false},{"id":483362,"name":"Daniel T. Chiu","orcid":"0000-0003-2964-9578","position":3,"is_corresponding":false},{"id":501227,"name":"Bertil Hille","orcid":"0000-0002-7266-1671","position":4,"is_corresponding":false},{"id":501226,"name":"Duk‐Su Koh","orcid":"0000-0003-0406-2308","position":5,"is_corresponding":false},{"id":501223,"name":"Seung‐Ryoung Jung","orcid":"0000-0002-1870-1433","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T23:47:53.089578Z","pmid":"33879605","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":[]}