Okamoto Shio, Chaya Taro, Omori Yoshihiro, Kuwahara Ryusuke, Kubo Shun, Sakaguchi Hirofumi, Furukawa Takahisa
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.
J Neurosci. 2017 Feb 22;37(8):2073-2085. doi: 10.1523/JNEUROSCI.3067-16.2017. Epub 2017 Jan 23.
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 of in 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. The 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.
细胞不对称性在发育和器官功能中起着关键作用。平面细胞极性（PCP）信号通路参与细胞片层平面内细胞不对称性的建立。内耳感觉毛细胞（HCs）具有几排阶梯状的静纤毛以及一根位于每个HC顶表面突出的静纤毛顶点处的动纤毛，呈现出典型的PCP形式。尽管在脊椎动物发育中已报道了纤毛与PCP信号之间的联系，但其确切性质尚不清楚。在内耳发育过程中，已知几种纤毛蛋白在PCP形成中起作用。在本研究中，我们研究了肠道细胞激酶（Ick）在小鼠内耳中的功能作用，Ick可调节纤毛顶端的鞭毛内运输（IFT）。发育中的内耳中Ick的缺失导致耳蜗中的PCP缺陷，包括静纤毛的方向错误或形态异常以及动纤毛和基体在顶转和中转中的异常定位，从而导致听觉功能障碍。我们还观察到Ift88在HCs和支持细胞中的纤毛定位异常。总之，我们的结果表明Ick纤毛激酶对于内耳HCs中的PCP形成至关重要，这表明纤毛运输调节对于PCP信号传导很重要。内耳中的耳蜗是听觉器官。耳蜗毛细胞（HCs）中的平面细胞极性（PCP）对于机械转导至关重要，是指由静纤毛束和细胞体顶表面上的动纤毛组成的不对称结构。我们之前报道过一种纤毛激酶Ick可调节鞭毛内运输（IFT）。在这里，我们发现Ick的缺失会导致动纤毛中IFT成分的定位异常、HCs中的PCP缺陷以及听力功能障碍。我们的研究确定了纤毛运输调节与HCs中PCP形成以及听力功能之间的关联。
