Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis.
Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis.
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DOI：
10.1038/s41598-018-23871-9
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发表时间：
2018-04-04
影响因子：
4.6
通讯作者：
Tewari R
中科院分区：
文献类型：
--
作者：
Wall RJ;Ferguson DJP;Freville A;Franke-Fayard B;Brady D;Zeeshan M;Bottrill AR;Wheatley S;Fry AM;Janse CJ;Yamano H;Holder AA;Guttery DS;Tewari R
后期促进复合物/环体（APC/C）是一种高度保守的多亚基E3泛素连接酶，通过标记细胞周期调节因子进行蛋白水解来控制真核细胞的有丝分裂。APC 3是APC/C功能的关键组成部分。疟原虫是疟疾的病原体，在其生命周期中经历非典型的有丝分裂。只有一小部分APC/C组分在疟原虫中被鉴定，它们参与非典型细胞分裂的情况还不清楚。在这里，使用反向遗传学，我们研究了APC 3在伯氏疟原虫中的定位和功能。APC 3被观察到作为一个单一的焦点，共定位与中心粒斑块在无性细胞分裂过程中的精子，而它出现在男性配子体的多个焦点。使用基因破坏和条件性敲低的功能研究揭示了APC 3在这些有丝分裂阶段的重要作用，其损失导致缺乏染色体凝聚、异常胞质分裂和缺乏小配子形成。总之，我们的数据表明，疟原虫利用独特的细胞周期机制，以协调各种过程中的有丝分裂，这在未来的研究中值得进一步调查。
The anaphase promoting complex/cyclosome (APC/C) is a highly conserved multi-subunit E3 ubiquitin ligase that controls mitotic division in eukaryotic cells by tagging cell cycle regulators for proteolysis. APC3 is a key component that contributes to APC/C function. Plasmodium, the causative agent of malaria, undergoes atypical mitotic division during its life cycle. Only a small subset of APC/C components has been identified in Plasmodium and their involvement in atypical cell division is not well understood. Here, using reverse genetics we examined the localisation and function of APC3 in Plasmodium berghei. APC3 was observed as a single focus that co-localised with the centriolar plaque during asexual cell division in schizonts, whereas it appeared as multiple foci in male gametocytes. Functional studies using gene disruption and conditional knockdown revealed essential roles of APC3 during these mitotic stages with loss resulting in a lack of chromosome condensation, abnormal cytokinesis and absence of microgamete formation. Overall, our data suggest that Plasmodium utilises unique cell cycle machinery to coordinate various processes during endomitosis, and this warrants further investigation in future studies.
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