{"doi":"10.1101/2020.02.20.958140","title":"Mechanistic Determinants of Slow Axonal Transport and Presynaptic Targeting of Clathrin Packets","abstract":"SUMMARY Clathrin has established roles in endocytosis, with clathrin-cages enclosing membrane infoldings, followed by rapid disassembly and reuse of monomers. However, in neurons, clathrin synthesized in cell-bodies is conveyed into axons and synapses via slow axonal transport; as shown by classic pulse-chase radiolabeling. What is the cargo-structure, and mechanisms underlying transport and presynaptic-targeting of clathrin? What is the precise organization at synapses? Combining live-imaging, mass-spectrometry (MS), Apex-labeled EM-tomography and super-resolution, we found that unlike dendrites where clathrin transiently assembles/disassembles as expected, axons contain stable ‘transport-packets’ that move intermittently with an anterograde bias; with actin/myosin-VI as putative tethers. Transport-packets are unrelated to endocytosis, and the overall kinetics generate a slow biased flow of axonal clathrin. Synapses have integer-numbers of clathrin-packets circumferentially abutting the synaptic-vesicle cluster, advocating a model where delivery of clathrin-packets by slow axonal transport generates a radial organization of clathrin at synapses. Our experiments reveal novel trafficking mechanisms, and an unexpected nanoscale organization of synaptic clathrin.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121975,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"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":0.9468,"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":562682,"name":"Florian Wernert","orcid":null,"position":1,"is_corresponding":false},{"id":326472,"name":"Sébastien Phan","orcid":"0000-0003-4261-6973","position":2,"is_corresponding":false},{"id":243104,"name":"Daniela Boassa","orcid":"0000-0003-4631-4139","position":3,"is_corresponding":false},{"id":562683,"name":"Utpal Das","orcid":null,"position":4,"is_corresponding":false},{"id":337219,"name":"Rohan Sharma","orcid":"0000-0002-3005-1867","position":5,"is_corresponding":false},{"id":562684,"name":"Ghislaine Caillol","orcid":null,"position":6,"is_corresponding":false},{"id":562685,"name":"Xuemei Han","orcid":null,"position":7,"is_corresponding":false},{"id":55408,"name":"John R. Yates","orcid":"0000-0001-5267-1672","position":8,"is_corresponding":false},{"id":227589,"name":"Mark H. Ellisman","orcid":"0000-0001-8893-8455","position":9,"is_corresponding":false},{"id":275198,"name":"Christophe Leterrier","orcid":"0000-0002-2957-2032","position":10,"is_corresponding":false},{"id":562201,"name":"Subhojit Roy","orcid":"0000-0002-1571-2735","position":11,"is_corresponding":false},{"id":300748,"name":"Archan Ganguly","orcid":"0000-0002-0351-9284","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:46.979435Z","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":[]}