PDF(Pubmed)
Abstract：
The Aurora family of kinases orchestrates chromosome segregation and cytokinesis during cell division, with precise spatiotemporal regulation of its catalytic activities by distinct protein scaffolds. Plasmodium spp., the causative agents of malaria, are unicellular eukaryotes with three unique and highly divergent aurora-related kinases (ARK1-3) that are essential for asexual cellular proliferation but lack most canonical scaffolds/activators. Here we investigate the role of ARK2 during sexual proliferation of the rodent malaria Plasmodium berghei, using a combination of super-resolution microscopy, mass spectrometry, and live-cell fluorescence imaging. We find that ARK2 is primarily located at spindle microtubules in the vicinity of kinetochores during both mitosis and meiosis. Interactomic and co-localisation studies reveal several putative ARK2-associated interactors including the microtubule-interacting protein EB1, together with MISFIT and Myosin-K, but no conserved eukaryotic scaffold proteins. Gene function studies indicate that ARK2 and EB1 are complementary in driving endomitotic division and thereby parasite transmission through the mosquito. This discovery underlines the flexibility of molecular networks to rewire and drive unconventional mechanisms of chromosome segregation in the malaria parasite.
摘要：
Aurora激酶家族在细胞分裂过程中协调染色体分离和胞质分裂，通过不同的蛋白质支架对其催化活性进行精确的时空调控。疟原虫。,疟疾的病原体，是单细胞真核生物，具有三种独特且高度不同的极光相关激酶（ARK1-3），对无性细胞增殖至关重要，但缺乏大多数规范的支架/激活剂。在这里，我们研究了ARK2在啮齿动物疟疾伯氏疟原虫的性增殖过程中的作用，使用超分辨率显微镜的组合，质谱,和活细胞荧光成像。我们发现，在有丝分裂和减数分裂期间，ARK2主要位于动子附近的纺锤体微管处。相互作用和共定位研究揭示了几种与ARK2相关的相互作用者，包括微管相互作用蛋白EB1，以及MISFIT和Myosin-K，但没有保守的真核支架蛋白。基因功能研究表明，ARK2和EB1在驱动有丝分裂分裂方面是互补的，从而通过蚊子传播寄生虫。这一发现强调了分子网络在疟疾寄生虫中重新连接和驱动非常规染色体分离机制的灵活性。
