Rsph9 is critical for ciliary radial spoke assembly and central pair microtubule stability
Rsph9 is critical for ciliary radial spoke assembly and central pair microtubule stability
复制标题
Rsph9 对于睫状径向辐条组装和中心对微管稳定性至关重要
DOI：
10.1111/boc.201800060
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发表时间：
2019
影响因子：
2.7
通讯作者：
Zhu Xueliang
中科院分区：
文献类型：
--
作者：
Zhu Lei;Liu Hao;Chen Yawen;Yan Xiumin;Zhu Xueliang
背景资料在“9+2”型运动纤毛中，放射状辐条（RSs）从9个外周微管双体中伸出，并与中心对（CP）装置相互作用，调节纤毛的搏动。RSPH9是主要原生动物RS头蛋白Rsp9的人类同源物。然而，它在人类原发性纤毛运动障碍患者中的突变导致一小部分气道纤毛CP丢失，而不影响其他头部蛋白的纤毛定位。结果对小鼠Rsph9进行了表征，并研究了其在室管膜运动性纤毛中的功能。Rsph9在含有运动纤毛的小鼠组织中特异性表达，并在多纤毛过程中上调。其纤毛定位符合其作为RS亚基的假定作用。RNAi在小鼠室管膜纤毛中缺失Rsph9导致CP几乎完全丧失，并使纤毛的搏动模式从平面变为旋转。多种RS蛋白，包括头部的RS蛋白，在Rsph9缺失的纤毛中也明显下调。结论rsph9对哺乳动物室管膜纤毛RS头组装和CP维持均有重要作用。意义本研究结果有助于了解哺乳动物RS的组装和功能以及RS相关纤毛病的病理。
Background InformationIn the “9+2”‐type motile cilia, radial spokes (RSs) protruded from the nine peripheral microtubule doublets surround and interact with the central pair (CP) apparatus to regulate ciliary beat. RSPH9 is the human homologue of the essential protozoan RS head protein Rsp9. Its mutations in human primary ciliary dyskinesia patients, however, cause CP loss in a small portion of airway cilia without affecting the ciliary localization of other head proteins.ResultsWe characterized mouse Rsph9 and investigated its function in ependymal motile cilia. Rsph9 was specifically expressed in mouse tissues containing motile cilia and upregulated during multiciliation. Its ciliary localization complied with its putative role as an RS subunit. Depletion of Rsph9 by RNAi in mouse ependymal cilia resulted in a near complete CP loss and altered the ciliary beat pattern from planar to rotational. Multiple RS proteins, including those in the head, were also markedly downregulated in the Rsph9‐depleted cilia.ConclusionRsph9 is essential for both the RS head assembly and the CP maintenance in mammalian ependymal cilia.SignificanceOur results help to understand the assembly and functions of mammalian RS and pathology of RS‐related ciliopathy.