Functional Analyses of Cytokinesis Regulators in Bloodstream Stage Trypanosoma brucei Parasites Identify Functions and Regulations Specific to the Life Cycle Stage
Functional Analyses of Cytokinesis Regulators in Bloodstream Stage Trypanosoma brucei Parasites Identify Functions and Regulations Specific to the Life Cycle Stage
复制标题
血流阶段布氏锥虫寄生虫细胞分裂调节因子的功能分析确定生命周期阶段特有的功能和调节
DOI：
10.1128/msphere.00199-19
复制
发表时间：
2019-05
期刊：
影响因子：
4.8
通讯作者：
Li Ziyin
中科院分区：
文献类型：
--
作者：
张玄;An Tai;Pham Kieu T. M.;伦照荣;Li Ziyin
早期发散的原生动物寄生虫布鲁氏锥虫是撒哈拉以南非洲人昏睡病和牛昏睡病的病原体。这种寄生虫有一个复杂的生活史，在昆虫媒介和哺乳动物宿主之间交替，并通过二元细胞分裂繁殖。锥虫对细胞分裂的控制似乎与人类宿主不同，并且在两个生命周期阶段--原环状(昆虫)和血流状--有很大不同。胞质分裂是二元细胞分裂的最后一步，由两个进化上保守的蛋白激酶和一组原循环形式的锥体特异性调节因子组成的新的信号级联系统调节，但这一信号通路是否在血流形式中以类似的方式工作尚不清楚。在这份报告中，我们对多种胞质分裂调节因子进行了功能分析，并发现了它们在血流形式中的不同功能和调节。摘要布氏锥虫是一种早期发散的原生动物，在其生活史中在昆虫媒介和哺乳动物宿主之间交替，并通过二元细胞分裂进行增殖。布氏毛滴虫的细胞周期控制系统与其哺乳动物的细胞周期控制系统有很大的不同，在原循环型和血流型两个生命周期阶段具有明显的有丝分裂-细胞质检查点控制。布氏锥虫经历了一种不寻常的胞质分裂模式，它由进化上保守的蛋白激酶和原环状锥虫特有的调节蛋白组成的新的信号级联系统控制。然而，鉴于这两种形式之间存在明显的有丝分裂-胞质分裂检查点，尚不清楚在原循环形式中发现的胞质分裂调节途径是否也在血流形式中以类似的方式工作。在这里，我们证明了胞质分裂启动的三个调节子，胞质启动因子1(CIF1)，CIF2和CIF3，对于亚细胞定位是相互依赖的，但不像在原环状形式中那样对于蛋白质稳定性是相互依赖的。此外，我们还证明了KLIF在血流形式的胞质分裂中的作用有限，KLIF是原环状的胞质分裂完成的调节因子。最后，我们证明了切割沟定位蛋白FRW1是启动血流形式胞质分裂所必需的，但对原循环形式的胞质分裂不是必需的。综上所述，这些结果确定了细胞质分裂调节因子的保守和生命周期特有的功能，突出了布鲁氏锥虫不同生活史阶段在胞质分裂调节方面的差异。重要性早期发散的原生动物寄生虫布鲁氏锥虫是撒哈拉以南非洲人昏睡病和牛昏睡病的病原体。这种寄生虫有一个复杂的生活史，在昆虫媒介和哺乳动物宿主之间交替，并通过二元细胞分裂繁殖。锥虫对细胞分裂的控制似乎与人类宿主不同，并且在两个生命周期阶段--原环状(昆虫)和血流状--有很大不同。胞质分裂是二元细胞分裂的最后一步，由两个进化上保守的蛋白激酶和一组原循环形式的锥体特异性调节因子组成的新的信号级联系统调节，但这一信号通路是否在血流形式中以类似的方式工作尚不清楚。在这份报告中，我们对多种胞质分裂调节因子进行了功能分析，并发现了它们在血流形式中的不同功能和调节。
The early divergent protozoan parasite Trypanosoma brucei is the causative agent of sleeping sickness in humans and nagana in cattle in sub-Saharan Africa. This parasite has a complex life cycle by alternating between the insect vector and the mammalian hosts and proliferates by binary cell fission. The control of cell division in trypanosomes appears to be distinct from that in its human host and differs substantially between two life cycle stages, the procyclic (insect) form and the bloodstream form. Cytokinesis, the final step of binary cell fission, is regulated by a novel signaling cascade consisting of two evolutionarily conserved protein kinases and a cohort of trypanosome-specific regulators in the procyclic form, but whether this signaling pathway operates in a similar manner in the bloodstream form is unclear. In this report, we performed a functional analysis of multiple cytokinesis regulators and discovered their distinct functions and regulations in the bloodstream form. ABSTRACT The early divergent protozoan parasite Trypanosoma brucei alternates between the insect vector and the mammalian hosts during its life cycle and proliferates through binary cell fission. The cell cycle control system in T. brucei differs substantially from that in its mammalian hosts and possesses distinct mitosis-cytokinesis checkpoint controls between two life cycle stages, the procyclic form and the bloodstream form. T. brucei undergoes an unusual mode of cytokinesis, which is controlled by a novel signaling cascade consisting of evolutionarily conserved protein kinases and trypanosome-specific regulatory proteins in the procyclic form. However, given the distinct mitosis-cytokinesis checkpoints between the two forms, it is unclear whether the cytokinesis regulatory pathway discovered in the procyclic form also operates in a similar manner in the bloodstream form. Here, we showed that the three regulators of cytokinesis initiation, cytokinesis initiation factor 1 (CIF1), CIF2, and CIF3, are interdependent for subcellular localization but not for protein stability as in the procyclic form. Further, we demonstrated that KLIF, a regulator of cytokinesis completion in the procyclic form, plays limited roles in cytokinesis in the bloodstream form. Finally, we showed that the cleavage furrow-localizing protein FRW1 is required for cytokinesis initiation in the bloodstream form but is nonessential for cytokinesis in the procyclic form. Together, these results identify conserved and life cycle-specific functions of cytokinesis regulators, highlighting the distinction in the regulation of cytokinesis between different life cycle stages of T. brucei. IMPORTANCE The early divergent protozoan parasite Trypanosoma brucei is the causative agent of sleeping sickness in humans and nagana in cattle in sub-Saharan Africa. This parasite has a complex life cycle by alternating between the insect vector and the mammalian hosts and proliferates by binary cell fission. The control of cell division in trypanosomes appears to be distinct from that in its human host and differs substantially between two life cycle stages, the procyclic (insect) form and the bloodstream form. Cytokinesis, the final step of binary cell fission, is regulated by a novel signaling cascade consisting of two evolutionarily conserved protein kinases and a cohort of trypanosome-specific regulators in the procyclic form, but whether this signaling pathway operates in a similar manner in the bloodstream form is unclear. In this report, we performed a functional analysis of multiple cytokinesis regulators and discovered their distinct functions and regulations in the bloodstream form.
登录
查看更多内容
影响因子：
3.7
作者：
Li Z;Lee JH;Chu F;Burlingame AL;Günzl A;Wang CC
通讯作者：
Wang CC
影响因子：
9.6
作者：
Sunter JD;Gull K
通讯作者：
Gull K
影响因子：
11.4
作者：
Kohl, L;Robinson, D;Bastin, P
通讯作者：
Bastin, P
影响因子：
4.8
作者：
Hammarton, TC;Clark, J;Mottram, JC
通讯作者：
Mottram, JC
影响因子：
4.8
作者：
Li, ZY;Zou, CB;Wang, CC
通讯作者：
Wang, CC