ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport

Authors

  • Taro Chaya,

    1. Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan
    2. JST, CREST, Suita, Osaka, Japan
    3. Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, Japan
    4. Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan
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  • Yoshihiro Omori,

    1. Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan
    2. JST, CREST, Suita, Osaka, Japan
    3. Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, Japan
    4. JST, PRESTO, Suita, Osaka, Japan
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  • Ryusuke Kuwahara,

    1. Research Center for Ultrahigh Voltage Electron Microscopy, Osaka University, Ibaraki, Osaka, Japan
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  • Takahisa Furukawa

    Corresponding author
    1. Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan
    2. JST, CREST, Suita, Osaka, Japan
    3. Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, Japan
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Abstract

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.

Synopsis

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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.

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