Bane Kartik S, Lepper Simone, Kehrer Jessica, Sattler Julia M, Singer Mirko, Reinig Miriam, Klug Dennis, Heiss Kirsten, Baum Jake, Mueller Ann-Kristin, Frischknecht Friedrich
Integrative Parasitology, Center for Infectious Diseases, University of Heidelberg Medical School, Heidelberg, Germany.
Parasitology, Center for Infectious Diseases, University of Heidelberg Medical School, Heidelberg, Germany.
PLoS Pathog. 2016 Jul 13;12(7):e1005710. doi: 10.1371/journal.ppat.1005710. eCollection 2016 Jul.
Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics.
引发疟疾的寄生虫需要迁移,以便穿透组织屏障并进入宿主细胞。在此我们表明,肌动蛋白丝结合蛋白冠蛋白调节伯氏疟原虫子孢子的滑行运动,子孢子是由蚊子传播的一种导致啮齿动物疟疾的寄生虫的高度运动形式。缺乏冠蛋白的寄生虫表现出运动缺陷,这损害了蚊子唾液腺的定殖,但不影响在皮肤中的迁移,然而会导致传播效率降低。在不运动的子孢子中,低钙浓度介导冠蛋白在肌动蛋白非依赖的情况下定位于外周。细胞外配体的结合触发细胞内钙释放,随后冠蛋白在肌动蛋白依赖的情况下重新定位于后方并启动运动。突变分析和成像表明,冠蛋白组织肌动蛋白丝以实现有效的运动。使用冠蛋白-樱桃荧光蛋白作为肌动蛋白丝存在的标记,我们发现蛋白激酶A有助于肌动蛋白丝的解体。我们最终推测,钙和cAMP介导的信号传导通过差异影响肌动蛋白动力学来调节从寄生虫快速运动到宿主细胞入侵的转换。