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PfCAP-H 对于疟原虫无性繁殖过程中凝聚素 I 复合物的组装和核分裂是必需的。

PfCAP-H is essential for assembly of condensin I complex and karyokinesis during asexual proliferation of .

机构信息

Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

mBio. 2024 May 8;15(5):e0285023. doi: 10.1128/mbio.02850-23. Epub 2024 Apr 2.

Abstract

UNLABELLED

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 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.

IMPORTANCE

Mitosis is a fundamental process for parasites, which plays a vital role in their survival within two distinct hosts-human and 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 spp., our understanding of how this complex is assembled and its precise functions during the blood stage development of remains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development of . 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

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凝缩蛋白 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的组装。有丝分裂凝缩蛋白 I 复合物的 kleisin 亚基 CAP-H 充当销子,以维持该复合物在有丝分裂染色体上的结构完整性和加载。该复合物存在于所有真核生物中,最近在 spp. 中也被鉴定出来。然而,这个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个复合物至关重要,仍有待探索。为了研究 PfCAP-H 在红细胞内细胞分裂过程中的作用,我们生成了一个可诱导的 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,在中期板处表达峰值最高。PfCAP-H 与 PfCAP-G 相互作用,是凝缩蛋白 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 缺陷型寄生虫中的有丝分裂纺锤体组装完好,但复制的中心体仍然聚集在未分割核的大量物质上,有丝分裂失败。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的凝缩蛋白 I 复合物的结构完整性方面发挥着关键作用,对疟原虫的无性发育至关重要。

重要性

有丝分裂对疟原虫来说是一个基本过程,在人类和 蚊子这两个截然不同的宿主中对其生存起着至关重要的作用。尽管它意义重大,但我们对有丝分裂及其调控的理解仍然有限。在真核生物中,有丝分裂受称为凝缩蛋白复合物的关键复合物之一调节。凝缩蛋白复合物负责染色体的浓缩,确保遗传物质忠实地分配到子细胞中。尽管最近在 spp. 中发现了凝缩蛋白复合物,但我们对该复合物如何组装及其在疟原虫血液阶段发育中的精确功能仍知之甚少。在这项研究中,我们研究了 PfCAP-H 在疟原虫血液阶段发育中的作用。我们的发现表明,PfCAP-H 是必不可少的,在维持凝缩蛋白 I 的结构和促进核分裂方面发挥着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6857/11078010/18a8e8e2761e/mbio.02850-23.f001.jpg

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