Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany.
Institute for Theoretical Physics and Bioquant, Heidelberg University, Heidelberg, Germany.
EMBO J. 2019 Aug 1;38(15):e100984. doi: 10.15252/embj.2018100984. Epub 2019 May 24.
Microtubules are cytoskeletal filaments essential for many cellular processes, including establishment and maintenance of polarity, intracellular transport, division and migration. In most metazoan cells, the number and length of microtubules are highly variable, while they can be precisely defined in some protozoan organisms. However, in either case the significance of these two key parameters for cells is not known. Here, we quantitatively studied the impact of modulating microtubule number and length in Plasmodium, the protozoan parasite causing malaria. Using a gene deletion and replacement strategy targeting one out of two α-tubulin genes, we show that chromosome segregation proceeds in the oocysts even in the absence of microtubules. However, fewer and shorter microtubules severely impaired the formation, motility and infectivity of Plasmodium sporozoites, the forms transmitted by the mosquito, which usually contain 16 microtubules. We found that α-tubulin expression levels directly determined the number of microtubules, suggesting a high nucleation barrier as supported by a mathematical model. Infectious sporozoites were only formed in parasite lines featuring at least 10 microtubules, while parasites with 9 or fewer microtubules failed to transmit.
微管是细胞骨架丝,对许多细胞过程至关重要,包括极性的建立和维持、细胞内运输、分裂和迁移。在大多数后生动物细胞中,微管的数量和长度变化很大,而在一些原生动物生物中可以精确定义。然而,在这两种情况下,这些两个关键参数对细胞的意义尚不清楚。在这里,我们定量研究了调节疟原虫(引起疟疾的原生动物寄生虫)中微管数量和长度的影响。使用针对两个α-微管蛋白基因之一的基因缺失和替换策略,我们表明即使没有微管,卵囊中的染色体分离也会进行。然而,更少和更短的微管严重损害了疟原虫子孢子的形成、运动和感染力,子孢子是通过蚊子传播的形式,通常含有 16 个微管。我们发现α-微管蛋白表达水平直接决定了微管的数量,这表明存在高成核障碍,这一观点得到了数学模型的支持。只有在具有至少 10 个微管的寄生虫系中才能形成感染性的子孢子,而具有 9 个或更少微管的寄生虫则无法传播。