ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport
ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport
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DOI：
10.1002/embj.201488175
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发表时间：
2014-06-02
期刊：
影响因子：
11.4
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
--
作者：
Chaya, Taro;Omori, Yoshihiro;Furukawa, Takahisa
纤毛和鞭毛由鞭毛内运输(IFT)形成和维持，在感知和跨物种移动方面发挥重要作用。在纤毛/鞭毛的远端，IFT复合体转过身来从顺行运输切换到逆行运输；然而，潜在的调控机制尚不清楚。在这里，我们确定了纤毛顶端的ICK定位是纤毛运输的调节器。在ick缺陷小鼠中，我们发现带有Hedgehog信号缺陷的神经前体细胞中存在纤毛缺陷。缺乏ICK的细胞形成带有错误定位的Hedgehog信号成分的纤毛。ICK的丧失导致了睫状体顶端IFT-A、IFT-B和BBB等成分的积累。相反，过度表达ICK诱导了IFT-B的强烈积累，但不能诱导IFT-A或BBB在纤毛尖的某些成分的积累。此外，ICK直接磷酸化Kif3a，而抑制这种Kif3a磷酸化会影响纤毛的形成。我们的结果表明，ICK是一种Kif3a激酶，通过调节纤毛顶端的纤毛运输，对发育过程中适当的纤毛发生是必不可少的。
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.