The surfaces of most cells in humans have small antenna-like structures termed cilia. There are two types of cilia: motile cilia and non-motile cilia. Motile cilia facilitate cell locomotion or fluid flow and non-motile cilia mediate cellular signaling, critically important for development. We are studying a specialized subcompartment of cilia, called the ciliary transition zone (TZ). The role of the TZ is to create a ‘barrier’ that controls the protein composition of the cilium, a function that is critical for the ability of the cilium to capture and transduce signals. In this study, we identified cyclin-dependent kinase-like 1 (CDKL-1) as a novel TZ protein. To our surprise, CDKL-1 is not associated with the formation of the TZ barrier, but instead, regulates ciliary length. We observe elongated cilia in cdkl-1 null ADL neurons, and shorter ADL cilia when CDKL-1 is overexpressed, indicating the correct level of this kinase is crucial for cilium length control. Mutations of human CDKL5, one of five CDKL family members, often cause human neurological disorders such as Rett syndrome and epilepsy, and most mutations are located in the conserved kinase domain of CDKL family members. We therefore introduced three of these mutations into C. elegans CDKL-1 (the only C. elegans CDKL family member). All CDKL-1 variants harboring the mutations failed to localize to the TZ, implicating that CDKL5 mutations may result in ciliary dysfunction in humans. Altogether, our results suggest that CDKL family members are ciliary proteins that regulate ciliary length and their dysfunction may lead to neurological phenotypes in humans.
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