PfCAP-H is essential for assembly of condensin I complex and karyokinesis during asexual proliferation of Plasmodium falciparum.
PfCAP-H is essential for assembly of condensin I complex and karyokinesis during asexual proliferation of Plasmodium falciparum.
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PfCAP-H 对于恶性疟原虫无性增殖过程中凝缩蛋白 I 复合物的组装和核分裂至关重要。
DOI：
10.1101/2024.02.26.582160
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Dvorin,JeffreyD
中科院分区：
文献类型：
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作者：
Gurung,Pratima;McGee,JamesP;Dvorin,JeffreyD
凝聚蛋白I是一种五聚体复合物，在真核生物中调节有丝分裂染色体装配。kleisin亚基CAP-H的凝聚素I复合物作为一个关键，以保持结构的完整性和加载的有丝分裂染色体上的这种复合物。这种复合体存在于所有真核生物中，最近在疟原虫属中被鉴定。然而，这种复合物是如何组装的，以及Kleisin亚基是否对这些寄生虫中的这种复合物至关重要，还有待探索。为了研究PfCAP-H在红细胞内细胞分裂期间的作用，我们产生了诱导型PfCAP-H敲除寄生虫。我们发现PfCAP-H在细胞有丝分裂过程中呈动态表达，在分裂中期板表达最高。PfCAP-H与PfCAP-G相互作用，是凝聚素I复合物的非SMC成员。值得注意的是，PfCAP-H的缺乏不会改变PfCAP-G的表达，但会影响其在有丝分裂染色体上的定位。虽然有丝分裂纺锤体组装是完整的PfCAP-H缺陷的寄生虫，重复的中心体仍然聚集在质量的未分割的核与失败的有丝分裂。这种失败导致异常核团的形成，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聚素I复合物的结构完整性方面起着至关重要的作用，并且对于疟原虫的无性发育是必不可少的。重要的是，有丝分裂是疟原虫的一个基本过程，它在疟原虫在两种不同的宿主-人和按蚊中的生存中起着至关重要的作用。尽管有丝分裂具有重要意义，但我们对它的理解及其调控仍然有限。在真核生物中，有丝分裂受一种称为缩合素复合物的关键复合物调节。凝聚素复合物负责染色体凝聚，确保遗传物质忠实地分配到子细胞。虽然最近在疟原虫属中鉴定了缩合素复合物，我们对这种复合物是如何组装的以及它在恶性疟原虫血液期发育过程中的精确功能的理解在很大程度上还没有被探索。在这项研究中，我们调查的中心蛋白，PfCAP-H，在血液阶段的发展P。恶性疟原虫。我们的研究结果表明，PfCAP-H是必不可少的，并且在维持凝聚素I的结构和促进有核分裂方面发挥着关键作用。
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 inPlasmodiumspp. 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.IMPORTANCEMitosis is a fundamental process forPlasmodiumparasites, which plays a vital role in their survival within two distinct hosts—human andAnophelesmosquitoes. 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 inPlasmodiumspp., our understanding of how this complex is assembled and its precise functions during the blood stage development ofPlasmodium falciparumremains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development ofP. falciparum. Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.