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Activation of the ciliary kinase CDKL5 is mediated by the cyclin-dependent kinase CDK20/LF2 to control flagellar length
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, Hou, Omi et al. 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. They 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 proteins, and controls phosphorylation of the tubulin-binding domain of IFT74, thereby influencing flagellar length. Mouse Cdkl5 shows similar properties. These results extend our understanding of ciliary length control. The image shows CDKL5 (green) concentrated near the base of mature flagella (red) of the unicellular green alga Chlamydomonas reinhardtii.
Image Credit: Yuqing Hou and Gregory Pazour
Citation: (2026) PLoS Biology Issue Image | Vol. 23(12) January 2026. PLoS Biol 23(12): ev23.i12. https://doi.org/10.1371/image.pbio.v23.i12
Published: January 13, 2026
Copyright: © 2026 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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, Hou, Omi et al. 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. They 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 proteins, and controls phosphorylation of the tubulin-binding domain of IFT74, thereby influencing flagellar length. Mouse Cdkl5 shows similar properties. These results extend our understanding of ciliary length control. The image shows CDKL5 (green) concentrated near the base of mature flagella (red) of the unicellular green alga Chlamydomonas reinhardtii.
Image Credit: Yuqing Hou and Gregory Pazour