{"doi":"10.1073/pnas.2503738122","title":"Dynamic early recruitment of GAK–Hsc70 regulates coated pit maturation","abstract":"Clathrin-mediated endocytosis (CME) begins with the assembly of clathrin onto the plasma membrane. These structures grow and stabilize to form clathrin-coated pits (CCPs), which invaginate and accumulate cargo. Finally, through membrane fission, CCPs detach to form clathrin-coated vesicles (CCVs). Mechanisms governing the transition of CCPs from flat-to-curved structures have been a matter of debate. GAK and its chaperone protein, Hsc70, are well known to mediate clathrin release from CCVs, and several studies have observed a late burst of GAK recruitment as CCVs form. Other studies have proposed that early recruitment of GAK-Hsc70 could function to provide the necessary energy source to remodel nascent flat clathrin lattices, replacing hexagons with pentagons and enabling a gain of curvature and invagination of the growing CCP; however, direct functional evidence is lacking. Here, we show that GAK knockdown inhibits CCP stabilization and invagination. Furthermore, mutations in the J domain of GAK that abolish Hsc70 recruitment to and activation at CCPs lead to the accumulation of GAK at CCPs, hinder CCP stabilization and invagination, and result in a striking increase in the proportion of highly transient, abortive CCPs. These findings support the hypothesis that GAK-Hsc70 promotes the turnover and remodeling of nascent clathrin assemblies required for curvature development during CME.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":518431,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9439,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1386311,"name":"Peiyao Zuo","orcid":null,"position":1,"is_corresponding":false},{"id":1386312,"name":"Peiliu Xu","orcid":null,"position":2,"is_corresponding":false},{"id":1386313,"name":"Haozhi Yuan","orcid":null,"position":3,"is_corresponding":false},{"id":340463,"name":"Madhura Bhave","orcid":"0000-0001-7446-9256","position":4,"is_corresponding":false},{"id":1385835,"name":"Xiangying Wei","orcid":"0000-0002-3731-7912","position":5,"is_corresponding":false},{"id":1385836,"name":"Ziyan Yang","orcid":"0009-0006-0378-0462","position":6,"is_corresponding":false},{"id":1152910,"name":"Lu Han","orcid":"0009-0002-0706-4157","position":7,"is_corresponding":false},{"id":274920,"name":"Sandra L. Schmid","orcid":"0000-0002-1690-7024","position":8,"is_corresponding":false},{"id":340460,"name":"Zhiming Chen","orcid":"0000-0002-2423-101X","position":9,"is_corresponding":false},{"id":1386310,"name":"Zhangping He","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:09.679930Z","pmid":"40424130","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":[]}