title: Ick Ciliary Kinase Is Essential for Planar Cell Polarity Formation in Inner Ear Hair Cells and Hearing Function.
abstract: Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells (HCs), which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood. During inner ear development, several ciliary proteins are known to play a role in PCP formation. In the current study, we investigated a functional role for intestinal cell kinase (Ick), which regulates intraflagellar transport (IFT) at the tip of cilia, in the mouse inner ear. A lack ofIckin the developing inner ear resulted in PCP defects in the cochlea, including misorientation or misshaping of stereocilia and aberrant localization of the kinocilium and basal body in the apical and middle turns, leading to auditory dysfunction. We also observed abnormal ciliary localization of Ift88 in both HCs and supporting cells. Together, our results show that Ick ciliary kinase is essential for PCP formation in inner ear HCs, suggesting that ciliary transport regulation is important for PCP signaling.SIGNIFICANCE STATEMENTThe cochlea in the inner ear is the hearing organ. Planar cell polarity (PCP) in hair cells (HCs) in the cochlea is essential for mechanotransduction and refers to the asymmetric structure consisting of stereociliary bundles and the kinocilium on the apical surface of the cell body. We reported previously that a ciliary kinase, Ick, regulates intraflagellar transport (IFT). Here, we found that loss of Ick leads to abnormal localization of the IFT component in kinocilia, PCP defects in HCs, and hearing dysfunction. Our study defines the association of ciliary transport regulation with PCP formation in HCs and hearing function.
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan.|Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, and.
authors.forename: Shio
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Chaya
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.affiliation: Research Center for Ultrahigh Voltage Electron Microscopy, Osaka University, Osaka, 567-0047, Japan.
authors.forename: Ryusuke
authors.identifier: 0000-0002-7041-0828
authors.initials: R
authors.lastname: Kuwahara
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Kubo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, and.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan, takahisa.furukawa@protein.osaka-u.ac.jp.
authors.forename: Takahisa
authors.identifier: 0000-0003-4171-220X
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics*; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006199:Hair Cells, Auditory, Inner / Q000502:physiology* / Q000648:ultrastructure; D006309:Hearing / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017084:Otoacoustic Emissions, Spontaneous / Q000235:genetics; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C086178:pericentrin; C000591805:Cilk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C486069:Dynll1 protein, rat; D056445:Cytoplasmic Dyneins
keywords: cilia; hearing function; inner ear; intraflagellar transport; kinase; planar cell polarity