{"doi":"10.1242/jcs.260327","title":"CCDC66 regulates primary cilium length and signaling via interactions with transition zone and axonemal proteins","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>The primary cilium is a microtubule-based organelle that serves as a hub for many signaling pathways. It functions as part of the centrosome or cilium complex, which also contains the basal body and the centriolar satellites. Little is known about the mechanisms by which the microtubule-based ciliary axoneme is assembled with a proper length and structure, particularly in terms of the activity of microtubule-associated proteins (MAPs) and the crosstalk between the different compartments of the centrosome or cilium complex. Here, we analyzed CCDC66, a MAP implicated in cilium biogenesis and ciliopathies. Live-cell imaging revealed that CCDC66 compartmentalizes between centrosomes, centriolar satellites, and the ciliary axoneme and tip during cilium biogenesis. CCDC66 depletion in human cells causes defects in cilium assembly, length and morphology. Notably, CCDC66 interacts with the ciliopathy-linked MAPs CEP104 and CSPP1, and regulates axonemal length and Hedgehog pathway activation. Moreover, CCDC66 is required for the basal body recruitment of transition zone proteins and intraflagellar transport B (IFT-B) machinery. Overall, our results establish CCDC66 as a multifaceted regulator of the primary cilium and provide insight into how ciliary MAPs and subcompartments cooperate to ensure assembly of functional cilia.</jats:p>","journal":"Journal of Cell Science","year":2023,"id":674816,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1518478,"name":"Deniz Conkar","orcid":"0000-0003-3374-8683","position":1,"is_corresponding":false},{"id":1518479,"name":"Jovana Deretic","orcid":"0000-0003-2003-1165","position":2,"is_corresponding":false},{"id":1399177,"name":"Umut Batman","orcid":"0000-0003-2591-6704","position":3,"is_corresponding":false},{"id":1518480,"name":"Kari-Anne M. Frikstad","orcid":"0000-0001-9923-3485","position":4,"is_corresponding":false},{"id":399412,"name":"Sebastian Patzke","orcid":"0000-0001-6821-197X","position":5,"is_corresponding":false},{"id":399621,"name":"Elif Nur Firat‐Karalar","orcid":"0000-0001-7589-473X","position":6,"is_corresponding":false},{"id":399619,"name":"Ezgi Odabasi","orcid":"0000-0002-9660-3062","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CCDC66 regulates primary cilium length and signaling via interactions with transition zone and axonemal proteins","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>The primary cilium is a microtubule-based organelle that serves as a hub for many signaling pathways. It functions as part of the centrosome or cilium complex, which also contains the basal body and the centriolar satellites. Little is known about the mechanisms by which the microtubule-based ciliary axoneme is assembled with a proper length and structure, particularly in terms of the activity of microtubule-associated proteins (MAPs) and the crosstalk between the different compartments of the centrosome or cilium complex. Here, we analyzed CCDC66, a MAP implicated in cilium biogenesis and ciliopathies. Live-cell imaging revealed that CCDC66 compartmentalizes between centrosomes, centriolar satellites, and the ciliary axoneme and tip during cilium biogenesis. CCDC66 depletion in human cells causes defects in cilium assembly, length and morphology. Notably, CCDC66 interacts with the ciliopathy-linked MAPs CEP104 and CSPP1, and regulates axonemal length and Hedgehog pathway activation. Moreover, CCDC66 is required for the basal body recruitment of transition zone proteins and intraflagellar transport B (IFT-B) machinery. Overall, our results establish CCDC66 as a multifaceted regulator of the primary cilium and provide insight into how ciliary MAPs and subcompartments cooperate to ensure assembly of functional cilia.</jats:p>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36606424","pmcid":null,"openalex_id":"https://openalex.org/W4313646662","authors":[],"funders":[{"funder_name":"H2020 Marie Skłodowska-Curie Actions","grant_id":"896644","title":"Resolving the mechanism of ciliary tip factors in primary and motile cilia assembly and function"},{"funder_name":"European Research Council","grant_id":"679140","title":"Dissecting the function and regulation of centriolar satellites: key regulators of the centrosome/cilium complex"},{"funder_name":"European Molecular Biology Organization","grant_id":"3622","title":null},{"funder_name":"Kreftforeningen","grant_id":"6839316","title":null},{"funder_name":"Türkiye Bilimsel ve Teknolojik Araştırma Kurumu","grant_id":"120C148","title":null}],"total_grants":5,"fwci":5.4993,"citation_percentile":0.96072063,"influential_citations":0,"citation_trend":[{"year":2023,"count":7},{"year":2024,"count":5},{"year":2025,"count":5},{"year":2026,"count":4}],"oa_status":"bronze","license":"http://www.biologists.com/user-licence-1-1/","oa_locations":[{"url":"https://journals.biologists.com/jcs/article-pdf/136/3/jcs260327/2468470/jcs260327.pdf","host_type":"journal"},{"url":"https://journals.biologists.com/jcs/article-pdf/136/3/jcs260327/2468470/jcs260327.pdf","host_type":"publisher"},{"url":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.260327/2414193/jcs260327.pdf","host_type":"publisher"},{"url":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.260327/2468470/jcs260327.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.260327","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36606424","host_type":"repository"},{"url":"https://aperta.ulakbim.gov.tr/record/267582","host_type":""},{"url":"http://dx.doi.org/10.1242/jcs.260327","host_type":""}],"fields_of_study":["Genetic and Kidney Cyst Diseases","Protist diversity and phylogeny","0301 basic medicine","03 medical and health sciences","Humans","Cilia","Axoneme","Hedgehog Proteins","Microtubule-Associated Proteins","Centrioles","Eye Proteins"],"mesh_terms":["Centrioles","Cilia","Eye Proteins","Humans","Microtubule-Associated Proteins","Hedgehog Proteins","Axoneme"],"keywords":["Cilium","Axoneme","Intraflagellar transport","Biology","Ciliopathies","Centrosome","Basal body","Cell biology","Ciliopathy","Ciliogenesis","Microtubule","Centriole","Microtubule organizing center","Motile cilium","Crosstalk","Flagellum","Genetics","Phenotype","Cell","Cell cycle","Primary Cilium","Centriolar Satellite","Ccdc66","Cilium Assembly","Humans","Hedgehog Proteins","Cilia","Eye Proteins","Microtubule-Associated Proteins","Centrioles"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T18:16:45.163647Z","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":[]}