NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1
NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1
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NudC 通过稳定丝切蛋白 1 来调节肌动蛋白动力学和纤毛发生
DOI：
10.1038/cr.2015.152
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发表时间：
2016
期刊：
影响因子：
44.1
通讯作者：
Tianhua Zhou
中科院分区：
文献类型：
--
作者：
Cheng Zhang;Wen Zhang;Yi Lu;Xiaoyi Yan;Xiumin Yan;Xueliang Zhu;Wei Liu;Yuehong Yang;Tianhua Zhou
新出现的数据表明，肌动蛋白动力学与纤毛发生相关。然而，其潜在机制仍不清楚。在此我们发现，核分布基因C（NudC），一种热休克蛋白90（Hsp90）的共伴侣蛋白，是肌动蛋白组织和动力学所必需的。NudC的缺失促进纤毛伸长，并增加有纤毛细胞的百分比。进一步的结果显示，NudC与肌动蛋白动力学的关键调节因子丝切蛋白1结合并使其稳定。丝切蛋白1的敲低也促进纤毛发生。此外，NudC或丝切蛋白1的缺失在斑马鱼中导致类似的纤毛缺陷，包括身体弯曲、心包水肿和左右不对称缺陷。丝切蛋白1的异位表达在培养细胞和斑马鱼中均显著逆转由NudC缺失诱导的表型。因此，我们的数据表明，NudC通过稳定丝切蛋白1来调节肌动蛋白细胞骨架和纤毛发生。
Emerging data indicate that actin dynamics is associated with ciliogenesis. However, the underlying mechanism remains unclear. Here we find that nuclear distribution gene C (NudC), an Hsp90 co-chaperone, is required for actin organization and dynamics. Depletion of NudC promotes cilia elongation and increases the percentage of ciliated cells. Further results show that NudC binds to and stabilizes cofilin 1, a key regulator of actin dynamics. Knockdown of cofilin 1 also facilitates ciliogenesis. Moreover, depletion of either NudC or cofilin 1 causes similar ciliary defects in zebrafish, including curved body, pericardial edema and defective left-right asymmetry. Ectopic expression of cofilin 1 significantly reverses the phenotypes induced by NudC depletion in both cultured cells and zebrafish. Thus, our data suggest that NudC regulates actin cytoskeleton and ciliogenesis by stabilizing cofilin 1.