Cilia and flagella are formed and maintained by intraflagellar transport (IFT) and play important roles in sensing and moving across species. At the distal tip of the cilia/flagella, IFT complexes turn around to switch from anterograde to retrograde transport; however, the underlying regulatory mechanism is unclear. Here, we identified ICK localization at the tip of cilia as a regulator of ciliary transport. In ICK-deficient mice, we found ciliary defects in neuronal progenitor cells with Hedgehog signal defects. ICK-deficient cells formed cilia with mislocalized Hedgehog signaling components. Loss of ICK caused the accumulation of IFT-A, IFT-B, and BBSome components at the ciliary tips. In contrast, overexpression of ICK induced the strong accumulation of IFT-B, but not IFT-A or BBSome components at ciliary tips. In addition, ICK directly phosphorylated Kif3a, while inhibition of this Kif3a phosphorylation affected ciliary formation. Our results suggest that ICK is a Kif3a kinase and essential for proper ciliogenesis in development by regulating ciliary transport at the tip of cilia.
Intestinal cell kinase (ICK) phosphorylates the kinesin-2 subunit Kif3a to regulate intraflagellar transport and therefore ciliary morphogenesis. ICK deficiency leads to cell type-specific loss of cilia and defective Sonic Hedgehog signaling during central nervous system development.
- Intestinal cell kinase (ICK) is essential for cell type-specific ciliogenesis and Hedgehog signaling in development.
- Ciliary transport is regulated by ICK at the tips of cilia.
- Kif3a is a phosphorylation target of ICK.
- Kif3a phosphorylation is required for normal ciliary formation.