Plasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages.
Plasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages.
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DOI：
10.1038/s41467-023-41395-3
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发表时间：
2023-09-13
影响因子：
16.6
通讯作者：
Tewari, Rita
中科院分区：
文献类型：
--
作者：
Zeeshan, Mohammad;Rea, Edward;Abel, Steven;Vukusic, Kruno;Markus, Robert;Brady, Declan;Eze, Antonius;Rashpa, Ravish;Balestra, Aurelia C.;Bottrill, Andrew R.;Brochet, Mathieu;Guttery, David S.;Tolic, Iva M.;Holder, Anthony A.;Le Roch, Karine G.;Tromer, Eelco C.;Tewari, Rita
Aurora激酶家族在细胞分裂期间协调染色体分离和胞质分裂，通过不同的蛋白质支架精确时空调节其催化活性。疟原虫属，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（ARK 1 -3），其对于无性细胞增殖是必需的，但缺乏大多数典型的支架/激活剂。在这里，我们调查ARK 2在啮齿动物伯氏疟原虫性增殖过程中的作用，使用超分辨率显微镜，质谱和活细胞荧光成像的组合。我们发现，ARK 2主要位于纺锤体微管附近的动粒在有丝分裂和减数分裂。Interactomic和co-localisation研究揭示了几个假定的ARK 2相关的相互作用，包括微管相互作用蛋白EB 1，连同MISFIT和肌球蛋白-K，但没有保守的真核支架蛋白。基因功能研究表明，ARK 2和EB 1是互补的驱动内有丝分裂，从而通过蚊子的寄生虫传播。这一发现强调了分子网络的灵活性，以重新布线和驱动疟疾寄生虫染色体分离的非常规机制。极光激酶协调染色体分离和细胞分裂。Zeeshan等人使用活细胞成像、蛋白质组学和功能遗传学研究了不同的疟原虫ARK 2和EB 1。这些是在传输阶段的非典型主轴动力学的关键组成部分。
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. The Aurora kinases orchestrate chromosome segregation and cell division. Zeeshan et al. studied divergent Plasmodium ARK2 and EB1 using live cell imaging, proteomics and functional genetics. These are critical components for atypical spindle dynamics during transmission stages.
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