{"doi":"10.1101/2022.06.16.496489","title":"Calcineurin associates with centrosomes and regulates cilia length maintenance","abstract":"Abstract Calcineurin, or PP2B, the Ca 2+ and calmodulin-activated phosphatase and target of immunosuppressants, has many substrates and functions that remain undiscovered. By combining rapid proximity-dependent labeling with cell cycle synchronization, we mapped calcineurin’s spatial distribution in different cell cycle stages. While calcineurin-proximal proteins did not vary significantly between interphase and mitosis, calcineurin consistently associated with multiple centrosomal/ciliary proteins. These include POC5, which binds centrin in a Ca 2+ -dependent manner and is a component of the luminal scaffold that stabilizes centrioles. We show that POC5 contains a calcineurin substrate motif (PxIxIT-type) that mediates calcineurin binding in vivo and in vitro . Using indirect immunofluorescence and expansion microscopy, we demonstrate that calcineurin co-localizes with POC5 at the centrosome, and further show that calcineurin inhibitors alter POC5 distribution within the centriole lumen. Our discovery that calcineurin directly associates with centrosomal proteins highlights a role for Ca 2+ and calcineurin signaling at these organelles. Calcineurin inhibition promotes primary cilia elongation without affecting ciliogenesis. Thus, Ca 2+ signaling within cilia includes previously unknown functions for calcineurin in cilia length maintenance, a process frequently disrupted in ciliopathies. Summary statement Calcineurin phosphatase participates in centrosome and cilia regulation. Calcineurin localizes to centrosomes, where it interacts with partner POC5, and its inhibition promotes cilia elongation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303608,"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":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":293140,"name":"Jennifer T. Wang","orcid":"0000-0002-8506-5182","position":1,"is_corresponding":false},{"id":269690,"name":"Cassandra J. Wong","orcid":"0009-0009-7292-3780","position":2,"is_corresponding":false},{"id":664676,"name":"Idil Ulengin-Talkish","orcid":"0000-0003-2809-4603","position":3,"is_corresponding":false},{"id":293145,"name":"Tim Stearns","orcid":"0000-0002-0671-6582","position":4,"is_corresponding":false},{"id":44860,"name":"Anne‐Claude Gingras","orcid":"0000-0002-6090-4437","position":5,"is_corresponding":false},{"id":263502,"name":"Martha Cyert","orcid":"0000-0003-3825-7437","position":6,"is_corresponding":false},{"id":293142,"name":"Eirini Tsekitsidou","orcid":"0000-0003-0946-9254","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","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":[]}