The trypanosome-specific protein CIF3 cooperates with the CIF1 protein to promote cytokinesis in Trypanosoma brucei
The trypanosome-specific protein CIF3 cooperates with the CIF1 protein to promote cytokinesis in Trypanosoma brucei
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DOI：
10.1074/jbc.ra118.003113
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发表时间：
2018-06-29
影响因子：
4.8
通讯作者：
Li, Ziyin
中科院分区：
文献类型：
--
作者：
Kurasawa, Yasuhiro;Hu, Huiqing;Li, Ziyin
人类原生病原体布鲁氏锥虫的细胞质分裂是细胞分裂的最后一步，它沿着新鞭毛附着带（FAZ）的前端向后端细胞尖端的纵轴进行。这一过程是由polo样激酶同源物TbPLK、Aurora B激酶同源物TbAUK1和锥虫特异性CIF1-CIF2蛋白复合物组成的信号级联调控的。然而，这种不寻常的细胞分裂模式的调控机制和信号通路仍然知之甚少。在这里，我们报道了另一种锥虫特异性蛋白质组装，CIF1-CIF3复合物，及其在细胞质分裂起始中的重要作用。通过生化和遗传学方法，我们证明了CIF3以tbplk依赖的方式与CIF1相互作用，并维持了CIF1在新FAZ尖端的定位。相反，CIF1在新的FAZ尖端保持了CIF3的稳定性。我们进一步证明TbPLK是CIF3定位所必需的，而CIF3是在后期将TbAUK1靶向到新的FAZ尖端所必需的。这些结果表明，两种含cif1的锥虫特异性蛋白复合物与进化上保守的polo样激酶和Aurora B激酶协同作用，促进了布氏锥虫的细胞分裂。
Cytokinesis, the terminal step in cell division, in the protist human pathogen Trypanosoma brucei occurs along the longitudinal axis from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior cell tip. This process is regulated by a signaling cascade composed of the Polo-like kinase homolog TbPLK, the Aurora B kinase homolog TbAUK1, and the trypanosome-specific CIF1-CIF2 protein complex. However, the regulatory mechanism and the signaling pathway for this unusual mode of cytokinesis remain poorly understood. Here, we report another trypanosome-specific protein assembly, the CIF1-CIF3 complex, and its essential role in cytokinesis initiation. Through biochemical and genetic approaches, we demonstrate that CIF3 interacts with CIF1 in a TbPLK-dependent manner and maintains CIF1 localization at the new FAZ tip. Conversely, CIF1 maintains CIF3 stability at the new FAZ tip. We further show that TbPLK is required for CIF3 localization and that CIF3 is necessary for targeting TbAUK1 to the new FAZ tip during anaphase. These results suggest that two trypanosome-specific CIF1-containing protein complexes cooperate with the evolutionarily conserved Polo-like kinase and Aurora B kinase to promote cytokinesis in T. brucei.