Ganter Markus, Schüler Herwig, Matuschewski Kai
Department of Parasitology, Heidelberg University School of Medicine, 69120 Heidelberg, Germany.
Mol Microbiol. 2009 Dec;74(6):1356-67. doi: 10.1111/j.1365-2958.2009.06828.x. Epub 2009 Aug 4.
Summary Successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. Sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. A unique feature of this motor machinery is the presence of very short subpellicular actin filaments. Therefore, F-actin stabilizing proteins likely play a central role in parasite locomotion. Here, we investigated the role of the Plasmodium berghei actin capping protein (PbCP), an orthologue of the heterodimeric regulator of filament barbed end growth, by reverse genetics. Parasites containing a deletion of the CP beta-subunit developed normally during the pathogenic erythrocytic cycle. However, due to reduced ookinete motility, mutant parasites form fewer oocysts and sporozoites in the Anopheles vector. These sporozoites display a vital deficiency in forward gliding motility and fail to colonize the mosquito salivary glands, resulting in complete attenuation of life cycle progression. Together, our results show that the CP beta-subunit exerts an essential role in the insect vector before malaria transmission to the mammalian host. The vital role is restricted to fast locomotion, as displayed by Plasmodium sporozoites.
摘要 疟原虫从蚊媒成功传播到哺乳动物宿主关键取决于子孢子的活跃运动性。子孢子的运动和宿主细胞入侵由寄生虫自身的肌动蛋白/肌球蛋白驱动。这种运动机制的一个独特特征是存在非常短的表膜下肌动蛋白丝。因此，F-肌动蛋白稳定蛋白可能在寄生虫运动中起核心作用。在这里，我们通过反向遗传学研究了伯氏疟原虫肌动蛋白封端蛋白（PbCP）的作用，它是丝状末端生长异二聚体调节因子的同源物。缺失CPβ亚基的寄生虫在致病性红细胞周期中正常发育。然而，由于动合子运动性降低，突变寄生虫在按蚊载体中形成的卵囊和子孢子较少。这些子孢子在前向滑行运动中表现出严重缺陷，无法在蚊唾液腺中定殖，导致生命周期进程完全减弱。总之，我们的结果表明，CPβ亚基在疟原虫传播到哺乳动物宿主之前在昆虫载体中发挥着重要作用。这一重要作用仅限于疟原虫子孢子所表现出的快速运动。
