The kinases male germ cell‐associated kinase and cell cycle‐related kinase regulate kinesin‐2 motility in Caenorhabditis elegans neuronal cilia

Kinesin‐2 motors power anterograde intraflagellar transport (IFT), a highly ordered process that assembles and maintains cilia. However, it remains elusive how kinesin‐2 motors are regulated in vivo. Here, we performed forward genetic screens to isolate suppressors that rescue the ciliary defects of OSM‐3‐kinesin (homolog of mammalian homodimeric kinesin‐2 KIF17) mutants in Caenorhabditis elegans. We identified the C. elegans dyf‐5 and dyf‐18, which encode the homologs of mammalian male germ cell‐associated kinase and cell cycle‐related kinase, respectively. Using time‐lapse fluorescence microscopy, we show that DYF‐5 and DYF‐18 are IFT cargo molecules and are enriched at the distal segments of sensory cilia. Mutations of dyf‐5 and dyf‐18 generate elongated cilia and ectopic localization of the heterotrimeric kinesin‐2 (kinesin‐II) at the ciliary distal segments. Genetic analyses reveal that dyf‐5 and dyf‐18 are important for stabilizing the interaction between IFT particles and OSM‐3‐kinesin. Our data suggest that DYF‐5 and DYF‐18 act in the same pathway to promote handover between kinesin‐II and OSM‐3 in sensory cilia.