{"doi":"10.7554/elife.107039","title":"CCDC32 stabilizes clathrin-coated pits and drives their invagination","abstract":"Clathrin-mediated endocytosis (CME) is essential for maintaining homeostasis in mammalian cells. Previous studies have reported more than 50 CME accessory proteins; however, the mechanism driving the invagination of clathrin-coated pits (CCPs) remains elusive. We show by quantitative live cell imaging that siRNA-mediated knockdown of CCDC32, a poorly characterized endocytic accessory protein, leads to the accumulation of unstable flat clathrin assemblies. CCDC32 interacts with the α-appendage domain (AD) of AP2 in vitro and with full-length AP2 complexes in cells. Deletion of aa78-98 in CCDC32, corresponding to a predicted α-helix, abrogates AP2 binding and CCDC32's early function in CME. Furthermore, clinically observed nonsense mutations in CCDC32, which result in C-terminal truncations that lack aa78-98, are linked to the development of cardio-facio-neuro-developmental syndrome (CFNDS). Overall, our data demonstrate the function of a novel endocytic accessory protein, CCDC32, in regulating CCP stabilization and invagination, critical early stages of CME.","journal":"eLife","year":2025,"id":567939,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"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":276493,"name":"Changsong Yang","orcid":null,"position":1,"is_corresponding":false},{"id":173184,"name":"Zheng Huang","orcid":null,"position":2,"is_corresponding":false},{"id":1386312,"name":"Peiliu Xu","orcid":null,"position":3,"is_corresponding":false},{"id":1176856,"name":"Yueping Li","orcid":"0009-0005-7134-5502","position":4,"is_corresponding":false},{"id":1152910,"name":"Lu Han","orcid":"0009-0002-0706-4157","position":5,"is_corresponding":false},{"id":1472459,"name":"Linyuan Peng","orcid":null,"position":6,"is_corresponding":false},{"id":1385835,"name":"Xiangying Wei","orcid":"0000-0002-3731-7912","position":7,"is_corresponding":false},{"id":104733,"name":"John E. Pak","orcid":"0000-0002-2998-9735","position":8,"is_corresponding":false},{"id":276495,"name":"Tatyana Svitkina","orcid":null,"position":9,"is_corresponding":false},{"id":274920,"name":"Sandra L. Schmid","orcid":"0000-0002-1690-7024","position":10,"is_corresponding":false},{"id":340460,"name":"Zhiming Chen","orcid":"0000-0002-2423-101X","position":11,"is_corresponding":false},{"id":1385836,"name":"Ziyan Yang","orcid":"0009-0006-0378-0462","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:56:48.183032Z","pmid":"41489497","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":[]}