{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hou Y"],"funding":["Li Weibo Institute for Rare Diseases Research","Loulou Foundation","University of Massachusetts Chan Medical School, Department of Radiology","National Institute of General Medical Sciences","NIGMS NIH HHS","NIH HHS"],"pagination":["e3003560"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12711092"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(12)"],"pubmed_abstract":["Variants in the protein kinase CDKL5 cause CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental condition characterized by seizures, developmental delay, and intellectual disability. The Chlamydomonas homolog of CDKL5, LF5, is a flagellar protein whose loss leads to elongated flagella. Here, we combine live-cell imaging, immunofluorescence, and biochemical approaches including mass spectrometry to define how CDKL5 activity is regulated and how its loss alters ciliary function. We find that Chlamydomonas CDKL5 is activated by LF2, a cyclin-dependent kinase, through phosphorylation of its activation loop. This activation controls CDKL5 localization in steady-state cilia, down-regulates its IFT-mediated transport as flagella reach steady-state, controls ciliary abundance of IFT protei"],"journal":["PLoS biology"],"pubmed_title":["Activation of the ciliary kinase CDKL5 is mediated by the cyclin-dependent kinase CDK20/LF2 to control flagellar length."],"pmcid":["PMC12711092"],"funding_grant_id":["R01 GM129325","R35 GM122574","P20 GM103449","GM060992","S10 OD028576","R01 GM060992","R35 GM152057","R35GM122574","R35GM152057"],"pubmed_authors":["Schmoker AM","Hou Y","Cheng X","Stuck MW","Omi OA","Walker B","Ballif BA","Witman GB","Gonzalez-Perez MP","Pazour GJ","Nguyen SN","Lechtreck KF","Lam YW"],"additional_accession":[]},"is_claimable":false,"name":"Activation of the ciliary kinase CDKL5 is mediated by the cyclin-dependent kinase CDK20/LF2 to control flagellar length.","description":"Variants in the protein kinase CDKL5 cause CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental condition characterized by seizures, developmental delay, and intellectual disability. The Chlamydomonas homolog of CDKL5, LF5, is a flagellar protein whose loss leads to elongated flagella. Here, we combine live-cell imaging, immunofluorescence, and biochemical approaches including mass spectrometry to define how CDKL5 activity is regulated and how its loss alters ciliary function. We find that Chlamydomonas CDKL5 is activated by LF2, a cyclin-dependent kinase, through phosphorylation of its activation loop. This activation controls CDKL5 localization in steady-state cilia, down-regulates its IFT-mediated transport as flagella reach steady-state, controls ciliary abundance of IFT protei","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-07-15T14:29:42.225Z","creation":"2026-07-06T03:08:55.349Z"},"accession":"S-EPMC12711092","cross_references":{"pubmed":["41385589"],"doi":["10.1371/journal.pbio.3003560"]}}