PDF(Pubmed)
Abstract：
Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replication, via a process called schizogony, is an important target for the development of new antimalarials. Here we use ultrastructure-expansion microscopy to probe the organisation of the chromosome-capturing kinetochores in relation to the mitotic spindle, the centriolar plaque, the centromeres and the apical organelles during schizont development. Conditional disruption of the kinetochore components, PfNDC80 and PfNuf2, is associated with aberrant mitotic spindle organisation, disruption of the centromere marker, CENH3 and impaired karyokinesis. Surprisingly, kinetochore disruption also leads to disengagement of the centrosome equivalent from the nuclear envelope. Severing the connection between the nucleus and the apical complex leads to the formation of merozoites lacking nuclei. Here, we show that correct assembly of the kinetochore/spindle complex plays a previously unrecognised role in positioning the nascent apical complex in developing P. falciparum merozoites.
摘要：
恶性疟原虫是疟疾的病原体，仍然是全球重要的病原体。无性血液阶段复制，通过一个叫做分裂的过程，是新型抗疟药物研发的重要靶点。在这里，我们使用超微结构扩展显微镜来探测与有丝分裂纺锤体相关的捕获染色体的组织，中心性斑块，裂殖体发育过程中的中心粒和顶端细胞器。运动细胞成分的有条件破坏，PfNDC80和PfNuf2与异常有丝分裂纺锤体组织有关，着丝粒标记的破坏，CENH3和核动力受损。令人惊讶的是,动粒的破坏也会导致中心体等效物从核壳中脱离。切断核与顶端复合体之间的连接会导致缺乏核的裂殖子的形成。这里,我们表明，动粒/纺锤体复合物的正确组装在发育中的恶性疟原虫裂殖子中定位新生的顶端复合物中起着以前未被认可的作用。
