{"doi":"10.1101/2020.12.28.424508","title":"Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9","abstract":"Summary Autophagy is a cellular degradation pathway essential for neuronal health and function. Autophagosome biogenesis occurs at synapses, is locally regulated and increases in response to neuronal activity. The mechanisms that couple autophagosome biogenesis to synaptic activity remain unknown. In this study we determine that trafficking of ATG-9, the only transmembrane protein in the core autophagy pathway, links the synaptic vesicle cycle with autophagy. ATG-9 positive vesicles in C. elegans are generated from the trans-Golgi network via AP3-dependent budding, and delivered to presynaptic sites. At presynaptic sites, ATG-9 undergoes exo-endocytosis in an activity-dependent manner. Mutations that disrupt endocytosis, including one associated with Parkinson’s disease, result in abnormal ATG-9 accumulation at clathrin-rich synaptic foci and defects in activity-dependent presynaptic autophagy. Our findings uncover regulated key steps of ATG-9 trafficking at presynaptic sites, and provide evidence that ATG-9 exo-endocytosis couples autophagosome biogenesis at presynaptic sites with the activity-dependent synaptic vesicle cycle. Highlights In C. elegans , ATG-9 is delivered to presynaptic sites in vesicles generated from the trans-Golgi network via AP-3-dependent budding ATG-9 vesicles undergo activity-dependent exo-endocytosis at presynaptic sites Mutations in endocytic proteins, including a mutation associated with Parkinson’s disease, result in abnormal ATG-9 accumulation at clathrin-rich foci Abnormal accumulation of ATG-9 at clathrin-rich foci is associated with defects in activity-dependent presynaptic autophagy","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122424,"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":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":350311,"name":"Daehun Park","orcid":"0000-0002-2829-1319","position":1,"is_corresponding":false},{"id":370313,"name":"Laura Manning","orcid":null,"position":2,"is_corresponding":false},{"id":238159,"name":"Sarah E. Hill","orcid":"0000-0002-8499-7455","position":3,"is_corresponding":false},{"id":350310,"name":"Mian Cao","orcid":"0000-0002-8519-6764","position":4,"is_corresponding":false},{"id":318610,"name":"Xuan Zhao","orcid":"0000-0002-8254-2887","position":5,"is_corresponding":false},{"id":318612,"name":"Ian Gonzalez","orcid":"0000-0002-2893-3713","position":6,"is_corresponding":false},{"id":304375,"name":"Lin Shao","orcid":"0000-0002-1905-4442","position":7,"is_corresponding":false},{"id":564114,"name":"Ifechukwu Okeke","orcid":null,"position":8,"is_corresponding":false},{"id":56624,"name":"Pietro De Camilli","orcid":"0000-0001-9045-0723","position":9,"is_corresponding":false},{"id":246611,"name":"Daniel A. Colón‐Ramos","orcid":"0000-0003-0223-7717","position":10,"is_corresponding":false},{"id":563577,"name":"Sisi Yang","orcid":"0000-0003-0352-833X","position":0,"is_corresponding":true}],"reference_count":113,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","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":[]}