title: ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport.
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.
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research Osaka University, Suita Osaka, Japan JST CREST, Suita Osaka, Japan Department of Developmental Biology, Osaka Bioscience Institute, Suita Osaka, Japan Kyoto University Graduate School of Medicine, Sakyo-ku Kyoto, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Chaya
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research Osaka University, Suita Osaka, Japan JST CREST, Suita Osaka, Japan Department of Developmental Biology, Osaka Bioscience Institute, Suita Osaka, Japan JST PRESTO, Suita Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.affiliation: Research Center for Ultrahigh Voltage Electron Microscopy Osaka University, Ibaraki Osaka, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Kuwahara
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research Osaka University, Suita Osaka, Japan JST CREST, Suita Osaka, Japan Department of Developmental Biology, Osaka Bioscience Institute, Suita Osaka, Japan takahisa.furukawa@protein.osaka-u.ac.jp.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000002:abnormalities; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005407:Flagella / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000002:abnormalities; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000166:cytology; D009928:Organ Specificity; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology; D015398:Signal Transduction; D013234:Stem Cells / Q000648:ultrastructure
chemical_list: D053823:Hedgehog Proteins; C490202:Kif3a protein, mouse; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins
keywords: ciliary transport; ciliogenesis; kinase; kinesin