Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation.
Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation.
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DOI：
10.1101/767830
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发表时间：
2019-09
影响因子：
4
通讯作者：
M. Zeeshan;R. Pandey;D. Ferguson;E. Tromer;Robert Markus;S. Abel;D. Brady;Emilie Daniel;R. Limenitakis;A. Bottrill;K. L. Le Roch;A. Holder;R. Waller;D. Guttery;R. Tewari
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文献类型：
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作者：
M. Zeeshan;R. Pandey;D. Ferguson;E. Tromer;Robert Markus;S. Abel;D. Brady;Emilie Daniel;R. Limenitakis;A. Bottrill;K. L. Le Roch;A. Holder;R. Waller;D. Guttery;R. Tewari
真核细胞的增殖需要染色体复制和精确分离，以确保子代细胞具有相同的基因组拷贝。疟原虫属是疟疾的病原体，在其整个生命周期中表现出显著的核分裂特征，以应对DNA复制和染色体分离的一些特殊和独特的挑战。该寄生虫经历了非典型的内有丝分裂和内复制，核膜完整，核内有丝分裂纺锤体。为了了解疟原虫细胞分裂的这些不同模式，我们研究了外部动粒NDC80复合体的行为和组成，NDC80复合体是有丝分裂装置的关键部分，将染色体的着丝粒附着在有丝分裂纺锤体的微管上。利用NDC80-GFP活细胞成像技术，我们观察了伯氏疟原虫增殖过程中的动态时空变化，包括有性阶段极不寻常的动粒排列。我们为NDC80复合体的SPC24亚基找到了一个非常不同的候选者，以前被认为在疟原虫中缺失，它完成了一个规范的，尽管不寻常的NDC80复合体结构。总之，我们的研究揭示了着丝粒是研究疟原虫染色体分离和细胞分裂的非规范模式的理想工具。
Eukaryotic cell proliferation requires chromosome replication and precise segregation to ensure daughter cells have identical genomic copies. The genus Plasmodium, the causative agent of malaria, displays remarkable aspects of nuclear division throughout its lifecycle to meet some peculiar and unique challenges of DNA replication and chromosome segregation. The parasite undergoes atypical endomitosis and endoreduplication with an intact nuclear membrane and intranuclear mitotic spindle. To understand these diverse modes of Plasmodium cell division, we have studied the behaviour and composition of the outer kinetochore NDC80 complex, a key part of the mitotic apparatus that attaches the centromere of chromosomes to microtubules of the mitotic spindle. Using NDC80-GFP live-cell imaging in Plasmodium berghei we observe dynamic spatiotemporal changes during proliferation, including highly unusual kinetochore arrangements during sexual stages. We identify a very divergent candidate for the SPC24 subunit of the NDC80 complex, previously thought to be missing in Plasmodium, which completes a canonical, albeit unusual, NDC80 complex structure. Altogether, our studies reveal the kinetochore as an ideal tool to investigate the non-canonical modes of chromosome segregation and cell division in Plasmodium.