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Abstract：
Condensin I is a pentameric complex that regulates the mitotic chromosome assembly in eukaryotes. The kleisin subunit CAP-H of the condensin I complex acts as a linchpin to maintain the structural integrity and loading of this complex on mitotic chromosomes. This complex is present in all eukaryotes and has recently been identified in Plasmodium spp. However, how this complex is assembled and whether the kleisin subunit is critical for this complex in these parasites are yet to be explored. To examine the role of PfCAP-H during cell division within erythrocytes, we generated an inducible PfCAP-H knockout parasite. We find that PfCAP-H is dynamically expressed during mitosis with the peak expression at the metaphase plate. PfCAP-H interacts with PfCAP-G and is a non-SMC member of the condensin I complex. Notably, the absence of PfCAP-H does not alter the expression of PfCAP-G but affects its localization at the mitotic chromosomes. While mitotic spindle assembly is intact in PfCAP-H-deficient parasites, duplicated centrosomes remain clustered over the mass of unsegmented nuclei with failed karyokinesis. This failure leads to the formation of an abnormal nuclear mass, while cytokinesis occurs normally. Altogether, our data suggest that PfCAP-H plays a crucial role in maintaining the structural integrity of the condensin I complex on the mitotic chromosomes and is essential for the asexual development of malarial parasites.
OBJECTIVE: Mitosis is a fundamental process for Plasmodium parasites, which plays a vital role in their survival within two distinct hosts-human and Anopheles mosquitoes. Despite its great significance, our comprehension of mitosis and its regulation remains limited. In eukaryotes, mitosis is regulated by one of the pivotal complexes known as condensin complexes. The condensin complexes are responsible for chromosome condensation, ensuring the faithful distribution of genetic material to daughter cells. While condensin complexes have recently been identified in Plasmodium spp., our understanding of how this complex is assembled and its precise functions during the blood stage development of Plasmodium falciparum remains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development of P. falciparum. Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.
OBJECTIVE: Mitosis is a fundamental process for Plasmodium parasites, which plays a vital role in their survival within two distinct hosts-human and Anopheles mosquitoes. Despite its great significance, our comprehension of mitosis and its regulation remains limited. In eukaryotes, mitosis is regulated by one of the pivotal complexes known as condensin complexes. The condensin complexes are responsible for chromosome condensation, ensuring the faithful distribution of genetic material to daughter cells. While condensin complexes have recently been identified in Plasmodium spp., our understanding of how this complex is assembled and its precise functions during the blood stage development of Plasmodium falciparum remains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development of P. falciparum. Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.
摘要：
凝结素I是调节真核生物有丝分裂染色体组装的五聚体复合物。凝缩素I复合物的kleisin亚基CAP-H充当关键，以维持该复合物在有丝分裂染色体上的结构完整性和负载。这种复合物存在于所有真核生物中，最近在疟原虫中被发现。然而,这种复合物是如何组装的，以及在这些寄生虫中，kleisin亚基是否对这种复合物至关重要，还有待探索。为了检查PfCAP-H在红细胞内细胞分裂过程中的作用，我们产生了可诱导的PfCAP-H敲除寄生虫。我们发现PfCAP-H在有丝分裂过程中动态表达，在中期板具有峰值表达。PfCAP-H与PfCAP-G相互作用并且是缩合蛋白I复合物的非SMC成员。值得注意的是,PfCAP-H的缺失不会改变PfCAP-G的表达，但会影响其在有丝分裂染色体上的定位。虽然PfCAP-H缺陷型寄生虫的有丝分裂纺锤体组装是完整的，重复的中心体仍然聚集在未分段的核团块上，核分裂失败。这种失败导致异常核质量的形成，而胞质分裂正常发生。总之,我们的数据表明PfCAP-H在维持有丝分裂染色体上凝集素I复合物的结构完整性中起着至关重要的作用,并且对于疟疾寄生虫的无性发育至关重要.
目的：有丝分裂是疟原虫寄生虫的基本过程，这对它们在两种不同的宿主——人类和按蚊中的生存起着至关重要的作用。尽管意义重大,我们对有丝分裂及其调节的理解仍然有限。在真核生物中,有丝分裂由称为凝缩素复合物的关键复合物之一调节。凝缩素复合物负责染色体缩合，确保遗传物质向子细胞的忠实分布。虽然最近在疟原虫中发现了凝缩素复合物。,我们对恶性疟原虫在血液阶段发育过程中这种复合物是如何组装的以及其确切功能的理解在很大程度上仍未被探索。在这项研究中,我们研究了中枢蛋白的作用，PfCAP-H,在恶性疟原虫的血液发育阶段。我们的发现表明，PfCAP-H是必不可少的，并且在维持凝集素I的结构和促进核分裂中起着关键作用。
目的：有丝分裂是疟原虫寄生虫的基本过程，这对它们在两种不同的宿主——人类和按蚊中的生存起着至关重要的作用。尽管意义重大,我们对有丝分裂及其调节的理解仍然有限。在真核生物中,有丝分裂由称为凝缩素复合物的关键复合物之一调节。凝缩素复合物负责染色体缩合，确保遗传物质向子细胞的忠实分布。虽然最近在疟原虫中发现了凝缩素复合物。,我们对恶性疟原虫在血液阶段发育过程中这种复合物是如何组装的以及其确切功能的理解在很大程度上仍未被探索。在这项研究中,我们研究了中枢蛋白的作用，PfCAP-H,在恶性疟原虫的血液发育阶段。我们的发现表明，PfCAP-H是必不可少的，并且在维持凝集素I的结构和促进核分裂中起着关键作用。
