Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia
Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia
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DOI：
10.1371/journal.pgen.1008664
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发表时间：
2020-03
期刊：
影响因子：
4.5
通讯作者：
Hiroshi Yoke;H. Ueno;A. Narita;Takafumi Sakai;K. Horiuchi;C. Shingyoji;H. Hamada;K. Shinohara
中科院分区：
文献类型：
--
作者：
Hiroshi Yoke;H. Ueno;A. Narita;Takafumi Sakai;K. Horiuchi;C. Shingyoji;H. Hamada;K. Shinohara
运动的纤毛/鞭毛对游泳和产生细胞外液流动在真核生物是必不可少的。活动纤毛呈9+2排列，由9个双线微管组成，动力蛋白臂位于外围，一对单线微管位于中心（中央对）。在中央系统中，径向辐条具有t形结构，并调节纤毛的运动和运动模式。最近的低温电子断层扫描数据显示，在96 nm轴突重复单元中存在三种类型的径向辐条（RS1、RS2和RS3）；然而，第三径向辐条RS3的分子组成是未知的。在人类病理学中，放射状辐头相关基因的突变导致原发性纤毛运动障碍（PCD），包括呼吸缺陷和不孕。在这里，我们描述了原发性纤毛运动障碍蛋白Rsph4a在小鼠运动性纤毛中的作用。低温电子断层扫描显示，与其他脊椎动物一样，小鼠气管纤毛有三种放射状辐条，而rsph4a缺陷小鼠的气管纤毛中缺乏所有的三联体辐条头。此外，纤毛运动观察和免疫荧光分析表明，Rsph4a通过在气管、室管膜组织和输卵管中建立径向辐条的远端结构，参与运动性纤毛平面跳动的产生。虽然Rsph4a组装的详细机制尚不清楚，但我们的研究结果表明Rsph4a是径向辐头的通用成分，可以解释人类PCD患者携带Rsph4a突变的严重表型。
Motile cilia/flagella are essential for swimming and generating extracellular fluid flow in eukaryotes. Motile cilia harbor a 9+2 arrangement consisting of nine doublet microtubules with dynein arms at the periphery and a pair of singlet microtubules at the center (central pair). In the central system, the radial spoke has a T-shaped architecture and regulates the motility and motion pattern of cilia. Recent cryoelectron tomography data reveal three types of radial spokes (RS1, RS2, and RS3) in the 96 nm axoneme repeat unit; however, the molecular composition of the third radial spoke, RS3 is unknown. In human pathology, it is well known mutation of the radial spoke head-related genes causes primary ciliary dyskinesia (PCD) including respiratory defect and infertility. Here, we describe the role of the primary ciliary dyskinesia protein Rsph4a in the mouse motile cilia. Cryoelectron tomography reveals that the mouse trachea cilia harbor three types of radial spoke as with the other vertebrates and that all triplet spoke heads are lacking in the trachea cilia of Rsph4a-deficient mice. Furthermore, observation of ciliary movement and immunofluorescence analysis indicates that Rsph4a contributes to the generation of the planar beating of motile cilia by building the distal architecture of radial spokes in the trachea, the ependymal tissues, and the oviduct. Although detailed mechanism of RSs assembly remains unknown, our results suggest Rsph4a is a generic component of radial spoke heads, and could explain the severe phenotype of human PCD patients with RSPH4A mutation.