{"doi":"10.1101/2024.03.04.583437","title":"N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine","abstract":"Abstract Post-translational modifications (PTMs) of α-synuclein (α-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Previously, we reported that α-syn clusters synaptic vesicles (SV) 1 , and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering 2 . Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological conditions and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn’s N-terminus and increased intermolecular interactions on the LPC-containing membrane. Our work demonstrates that N-acetylation fine-tunes α-syn–LPC interaction for mediating α-syn’s function in SV clustering.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490245,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":759836,"name":"Chunyu Zhao","orcid":"0000-0003-0168-2130","position":1,"is_corresponding":false},{"id":1045263,"name":"Xiao Hu","orcid":"0000-0001-9133-3705","position":2,"is_corresponding":false},{"id":482956,"name":"Jiali Qiang","orcid":"0000-0001-6108-498X","position":3,"is_corresponding":false},{"id":236986,"name":"Zhenying Liu","orcid":"0000-0002-0035-7486","position":4,"is_corresponding":false},{"id":806813,"name":"Jinge Gu","orcid":"0000-0001-5219-5821","position":5,"is_corresponding":false},{"id":482964,"name":"Shengnan Zhang","orcid":"0000-0003-1051-7196","position":6,"is_corresponding":false},{"id":236990,"name":"Dan Li","orcid":"0000-0002-1609-1539","position":7,"is_corresponding":false},{"id":482963,"name":"Yaoyang Zhang","orcid":"0000-0001-5363-9834","position":8,"is_corresponding":false},{"id":814165,"name":"Jacqueline Burré","orcid":"0000-0001-8968-248X","position":9,"is_corresponding":false},{"id":281294,"name":"Jiajie Diao","orcid":"0000-0003-4288-3203","position":10,"is_corresponding":false},{"id":236995,"name":"Cong Liu","orcid":"0000-0003-3425-6672","position":11,"is_corresponding":false},{"id":482959,"name":"Chuchu Wang","orcid":"0000-0003-2015-7331","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38496494","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":[]}