Functional analyses of an axonemal inner-arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation
Functional analyses of an axonemal inner-arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation
复制标题
对布氏锥虫血流形式中轴丝内臂动力蛋白复合物的功能分析揭示了其在胞质分裂启动中的重要作用
DOI：
10.1111/mmi.14385
复制
发表时间：
2019
影响因子：
3.6
通讯作者：
Li Ziyin
中科院分区：
文献类型：
--
作者：
张玄;Hu Huiqing;伦照荣;Li Ziyin
有鞭毛的真核四核体在昆虫载体和哺乳动物宿主之间交替，并通过一种不寻常的细胞分裂模式进行增殖。细胞分裂需要鞭毛运动产生的力量，但鞭毛运动在不同的生命周期形式中具有不同的作用。运动是昆虫载体中原环形式的细胞最终脱落所必需的，但对于哺乳动物宿主中血流形式的细胞分裂的开始是必要的。潜在的机制仍然难以捉摸。在这里，我们对鞭毛轴突内臂动力蛋白复合物在血流形态中的功能进行了分析，并研究了其在细胞分裂起始中的机制作用。我们发现轴突内臂动力蛋白重链TbIAD5 - 1和TbCentrin3形成一个复合物，定位于鞭毛，并且是血液形式生存所必需的。我们进一步证明了TbIAD5‐1和TbCentrin3在维持蛋白稳定性方面的相互依赖性。最后，我们发现TbIAD5‐1和TbCentrin3的缺失阻止了细胞分裂起始，并破坏了多个细胞分裂起始调节因子的定位。这些发现确定了轴突内臂动力蛋白复合物在细胞分裂中的重要作用，并提供了鞭毛运动介导的ofT血流中细胞分裂起始的分子见解。brucei。
The flagellated eukaryoteTrypanosoma bruceialternates between the insect vector and the mammalian host and proliferates through an unusual mode of cell division. Cell division requires flagellum motility‐generated forces, but flagellum motility exerts distinct effects between different life cycle forms. Motility is required for the final cell abscission of the procyclic form in the insect vector, but is necessary for the initiation of cell division of the bloodstream form in the mammalian host. The underlying mechanisms remain elusive. Here we carried out functional analyses of a flagellar axonemal inner‐arm dynein complex in the bloodstream form and investigated its mechanistic role in cytokinesis initiation. We showed that the axonemal inner‐arm dynein heavy chain TbIAD5‐1 and TbCentrin3 form a complex, localize to the flagellum, and are required for viability in the bloodstream form. We further demonstrated the interdependence between TbIAD5‐1 and TbCentrin3 for maintenance of protein stability. Finally, we showed that depletion of TbIAD5‐1 and TbCentrin3 arrested cytokinesis initiation and disrupted the localization of multiple cytokinesis initiation regulators. These findings identified the essential role of an axonemal inner‐arm dynein complex in cell division, and provided molecular insights into the flagellum motility‐mediated cytokinesis initiation in the bloodstream form ofT. brucei.