Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.
Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
PLoS Pathog. 2023 May 2;19(5):e1011325. doi: 10.1371/journal.ppat.1011325. eCollection 2023 May.
Malaria-causing parasites achieve rapid proliferation in human blood through multiple rounds of asynchronous nuclear division followed by daughter cell formation. Nuclear divisions critically depend on the centriolar plaque, which organizes intranuclear spindle microtubules. The centriolar plaque consists of an extranuclear compartment, which is connected via a nuclear pore-like structure to a chromatin-free intranuclear compartment. Composition and function of this non-canonical centrosome remain largely elusive. Centrins, which reside in the extranuclear part, are among the very few centrosomal proteins conserved in Plasmodium falciparum. Here we identify a novel centrin-interacting centriolar plaque protein. Conditional knock down of this Sfi1-like protein (PfSlp) caused a growth delay in blood stages, which correlated with a reduced number of daughter cells. Surprisingly, intranuclear tubulin abundance was significantly increased, which raises the hypothesis that the centriolar plaque might be implicated in regulating tubulin levels. Disruption of tubulin homeostasis caused excess microtubules and aberrant mitotic spindles. Time-lapse microscopy revealed that this prevented or delayed mitotic spindle extension but did not significantly interfere with DNA replication. Our study thereby identifies a novel extranuclear centriolar plaque factor and establishes a functional link to the intranuclear compartment of this divergent eukaryotic centrosome.
疟原虫在人体血液中通过多轮非同步核分裂和子细胞形成实现快速增殖。核分裂严重依赖于中心粒斑,它组织核内纺锤体微管。中心粒斑由一个核外隔室组成,通过类似于核孔的结构与无染色质的核内隔室相连。这个非典型中心体的组成和功能在很大程度上仍然难以捉摸。位于核外部分的中心体蛋白是疟原虫中少数保守的中心体蛋白之一。在这里,我们鉴定了一种新型的中心体蛋白与中心粒斑相互作用的蛋白。该蛋白(PfSlp)条件性敲低会导致血期生长延迟,与子细胞数量减少相关。令人惊讶的是,核内微管蛋白的丰度显著增加,这提出了中心粒斑可能参与调节微管蛋白水平的假说。微管平衡的破坏导致了过多的微管和异常的有丝分裂纺锤体。延时显微镜观察显示,这阻止或延迟了有丝分裂纺锤体的延伸,但并没有显著干扰 DNA 复制。因此,我们的研究鉴定了一种新型的核外中心粒斑因子,并建立了与这种具有差异性的真核中心体的核内隔室的功能联系。