The Modular Circuitry of Apicomplexan Cell Division Plasticity.

The Modular Circuitry of Apicomplexan Cell Division Plasticity.
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DOI:
10.3389/fcimb.2021.670049
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发表时间:
2021
影响因子:
5.7
通讯作者:
Engelberg K
Engelberg K
中科院分区:
医学2区
文献类型:
--
作者:
Gubbels MJ;Coppens I;Zarringhalam K;Duraisingh MT;Engelberg K

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顶复门寄生虫的紧密结合组显示出各种各样的细胞分裂模式,这些模式在寄生虫之间以及在单个寄生虫物种内的不同生命阶段之间是不同的。无性复制周期的起点和终点是一个“子实体”,其中含有宿主细胞入侵所需的定义顶端细胞器。然而,每一轮分裂产生的子实体的数量变化很大,可以以几种不同的方式展开。细胞分裂周期的这种可塑性源于由环境触发器调制的硬连线发育程序的组合。虽然环境触发器和传感器不同物种和发育阶段,广泛保守的第二信使介导的信号转导途径。这些环境和遗传输入整合在分裂模式特异性染色体组织和染色质修饰中,为每个分裂模式设置了阶段。细胞周期进程是由积极和消极作用的转录因子的自助餐传达的,这些转录因子通常与表观遗传阅读器复合物协同作用,这些转录因子在物种之间以及分裂模式之间可能会发生巨大变化。一组独特的细胞周期调节因子,具有空间上不同的定位模式,插入离散的检查点,允许单独控制,并可以从核扩增中解耦一般细胞周期进程。表达基因的簇被分成四个功能模块,在所有分裂模式中都可以看到:1。母细胞骨架解体; 2. DNA复制和分离(D&S); 3.有丝分裂; 4. zoite装配一个即插即用的战略结果在各种各样的现存的分工模式。母细胞骨架解体的时间在物种水平上对于无性分裂模式是固定的:它要么是第一步,要么是最后一步。在前一种情况下,子孢子组装发生在质膜上(外部出芽),而在后一种情况下,子孢子组装在细胞质中(内部出芽)。每个其他模块重复的次数可以变化,而不管这个第一个决定,并定义了细胞分裂的模式:同源生殖,二分裂,endodysis,endopolygeny。
The close-knit group of apicomplexan parasites displays a wide variety of cell division modes, which differ between parasites as well as between different life stages within a single parasite species. The beginning and endpoint of the asexual replication cycles is a ‘zoite’ harboring the defining apical organelles required for host cell invasion. However, the number of zoites produced per division round varies dramatically and can unfold in several different ways. This plasticity of the cell division cycle originates from a combination of hard-wired developmental programs modulated by environmental triggers. Although the environmental triggers and sensors differ between species and developmental stages, widely conserved secondary messengers mediate the signal transduction pathways. These environmental and genetic input integrate in division-mode specific chromosome organization and chromatin modifications that set the stage for each division mode. Cell cycle progression is conveyed by a smorgasbord of positively and negatively acting transcription factors, often acting in concert with epigenetic reader complexes, that can vary dramatically between species as well as division modes. A unique set of cell cycle regulators with spatially distinct localization patterns insert discrete check points which permit individual control and can uncouple general cell cycle progression from nuclear amplification. Clusters of expressed genes are grouped into four functional modules seen in all division modes: 1. mother cytoskeleton disassembly; 2. DNA replication and segregation (D&S); 3. karyokinesis; 4. zoite assembly. A plug-and-play strategy results in the variety of extant division modes. The timing of mother cytoskeleton disassembly is hard-wired at the species level for asexual division modes: it is either the first step, or it is the last step. In the former scenario zoite assembly occurs at the plasma membrane (external budding), and in the latter scenario zoites are assembled in the cytoplasm (internal budding). The number of times each other module is repeated can vary regardless of this first decision, and defines the modes of cell division: schizogony, binary fission, endodyogeny, endopolygeny.