c21orf59/kurly Controls Both Cilia Motility and Polarization

Cilia are microtubule-based projections that function in the movement of extracellular fluid. This requires cilia to be: (1) motile and driven by dynein complexes and (2) correctly polarized on the surface of cells, which requires planar cell polarity (PCP). Few factors that regulate both processes have been discovered. We reveal that C21orf59/Kurly (Kur), a cytoplasmic protein with some enrichment at the base of cilia, is needed for motility; zebrafish mutants exhibit characteristic developmental abnormalities and dynein arm defects. kur was also required for proper cilia polarization in the zebrafish kidney and the larval skin of Xenopus laevis. CRISPR/Cas9 coupled with homologous recombination to disrupt the endogenous kur locus in Xenopus resulted in the asymmetric localization of the PCP protein Prickle2 being lost in mutant multiciliated cells. Kur also makes interactions with other PCP components, including Disheveled. This supports a model wherein Kur plays a dual role in cilia motility and polarization. [Display omitted] •kurly (kur) mutants exhibit defects characteristic of motile cilia dysfunction•c21orf59 is mutated in kur and is needed for dynein arm localization/cilia motility•CRISPR/Cas9 with homologous recombination in Xenopus shows C21orf59 regulates PCP•C21orf59 interacts with various PCP components to correctly polarize motile cilia Jaffe et al. report a dual role for the C21orf59 protein in cilia motility and polarization. Zebrafish and Xenopus mutants revealed motility and planar cell polarity (PCP) as well as cilia positioning defects. C21orf59 made several interactions with PCP components and was required for proper Prickle2 localization.