{"doi":"10.1101/2023.11.01.565151","title":"Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons","abstract":"Summary Cilia-derived extracellular vesicles (EVs) contain signaling proteins and act in intercellular communication. Polycystin-2 (PKD-2), a transient receptor potential channel, is a conserved ciliary EVs cargo. Caenorhabditis elegans serves as a model for studying ciliary EV biogenesis and function. C. elegans males release EVs in a mechanically-induced manner and deposit PKD-2-labeled EVs onto the hermaphrodite vulva during mating, suggesting an active release process. Here, we study the dynamics of ciliary EV release using time-lapse imaging and find that cilia can sustain the release of PKD-2-labeled EVs for a two-hour duration. Intriguingly, this extended release doesn’t require neuronal synaptic transmission. Instead, ciliary intrinsic mechanisms regulate PKD-2 ciliary membrane replenishment and dynamic EV release. The ciliary kinesin-3 motor KLP-6 is necessary for both initial and extended ciliary EV release, while the transition zone protein NPHP-4 is required only for sustained EV release. The dihydroceramide desaturase DEGS1/2 ortholog TTM-5 is highly expressed in the EV-releasing sensory neurons, localizes to cilia, and is required for sustained but not initial ciliary EV release, implicating ceramide in ciliary ectocytosis. The study offers a comprehensive portrait of real-time ciliary EV release, and mechanisms supporting cilia as proficient EV release platforms.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393797,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":828909,"name":"Josh Saul","orcid":null,"position":1,"is_corresponding":false},{"id":353205,"name":"Inna A. Nikonorova","orcid":"0000-0001-8498-848X","position":2,"is_corresponding":false},{"id":1168294,"name":"Carlos Nava Cruz","orcid":null,"position":3,"is_corresponding":false},{"id":495293,"name":"Kaiden M. Power","orcid":"0000-0002-2615-2294","position":4,"is_corresponding":false},{"id":345354,"name":"Ken C. Q. Nguyen","orcid":"0000-0002-3479-2611","position":5,"is_corresponding":false},{"id":310868,"name":"David H. Hall","orcid":"0000-0001-8459-9820","position":6,"is_corresponding":false},{"id":345359,"name":"Maureen M. Barr","orcid":"0000-0003-4483-2952","position":7,"is_corresponding":false},{"id":274538,"name":"Juan Wang","orcid":"0000-0003-1992-0539","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:19:05.913428Z","pmid":"37961114","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":[]}