Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY PLoS Biology Pub Date : 2024-09-10 DOI:10.1371/journal.pbio.3002802
Mohammad Zeeshan, Ravish Rashpa, David J. Ferguson, George Mckeown, Raushan Nugmanova, Amit K. Subudhi, Raphael Beyeler, Sarah L. Pashley, Robert Markus, Declan Brady, Magali Roques, Andrew R. Bottrill, Andrew M. Fry, Arnab Pain, Sue Vaughan, Anthony A. Holder, Eelco C. Tromer, Mathieu Brochet, Rita Tewari
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Abstract

Mitosis is an important process in the cell cycle required for cells to divide. Never in mitosis (NIMA)-like kinases (NEKs) are regulators of mitotic functions in diverse organisms. Plasmodium spp., the causative agent of malaria is a divergent unicellular haploid eukaryote with some unusual features in terms of its mitotic and nuclear division cycle that presumably facilitate proliferation in varied environments. For example, during the sexual stage of male gametogenesis that occurs within the mosquito host, an atypical rapid closed endomitosis is observed. Three rounds of genome replication from 1N to 8N and successive cycles of multiple spindle formation and chromosome segregation occur within 8 min followed by karyokinesis to generate haploid gametes. Our previous Plasmodium berghei kinome screen identified 4 Nek genes, of which 2, NEK2 and NEK4, are required for meiosis. NEK1 is likely to be essential for mitosis in asexual blood stage schizogony in the vertebrate host, but its function during male gametogenesis is unknown. Here, we study NEK1 location and function, using live cell imaging, ultrastructure expansion microscopy (U-ExM), and electron microscopy, together with conditional gene knockdown and proteomic approaches. We report spatiotemporal NEK1 location in real-time, coordinated with microtubule organising centre (MTOC) dynamics during the unusual mitoses at various stages of the Plasmodium spp. life cycle. Knockdown studies reveal NEK1 to be an essential component of the MTOC in male cell differentiation, associated with rapid mitosis, spindle formation, and kinetochore attachment. These data suggest that P. berghei NEK1 kinase is an important component of MTOC organisation and essential regulator of chromosome segregation during male gamete formation.
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疟原虫 NEK1 在雄配子形成的快速有丝分裂过程中协调 MTOC 组织和着丝点附着
有丝分裂是细胞分裂所需的细胞周期中的一个重要过程。绝不有丝分裂(NIMA)样激酶(NEKs)是多种生物有丝分裂功能的调节因子。疟疾的致病菌疟原虫是一种分化的单细胞单倍体真核生物,其有丝分裂和核分裂周期具有一些不同寻常的特征,这些特征可能有利于其在不同环境中增殖。例如,在蚊子宿主体内雄性配子发生的有性阶段,观察到一种非典型的快速封闭内配现象。在 8 分钟内进行了从 1N 到 8N 的三轮基因组复制,以及连续的多纺锤体形成和染色体分离循环,然后进行核运动,产生单倍体配子。我们之前的疟原虫激酶组筛选发现了 4 个 Nek 基因,其中 NEK2 和 NEK4 这两个基因是减数分裂所必需的。在脊椎动物宿主的无性血液阶段分裂过程中,NEK1可能是有丝分裂所必需的,但其在雄性配子发生过程中的功能尚不清楚。在这里,我们利用活细胞成像、超微结构扩展显微镜(U-ExM)和电子显微镜,以及条件基因敲除和蛋白质组学方法研究了 NEK1 的位置和功能。我们实时报告了 NEK1 在疟原虫生命周期各阶段不寻常有丝分裂过程中与微管组织中心(MTOC)动态相协调的时空位置。基因敲除研究显示 NEK1 是雄性细胞分化过程中 MTOC 的重要组成部分,与快速有丝分裂、纺锤体形成和动核附着有关。这些数据表明,疟原虫 NEK1 激酶是 MTOC 组织的重要组成部分,也是雄配子形成过程中染色体分离的重要调节因子。
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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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