The Actin Filament-Binding Protein Coronin Regulates Motility in Plasmodium Sporozoites
The Actin Filament-Binding Protein Coronin Regulates Motility in Plasmodium Sporozoites
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DOI：
10.1371/journal.ppat.1005710
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发表时间：
2016-07-01
期刊：
影响因子：
6.7
通讯作者：
Frischknecht, Friedrich
中科院分区：
文献类型：
--
作者：
Bane, Kartik S.;Lepper, Simone;Frischknecht, Friedrich
引起疟疾的寄生虫需要迁移以穿透组织屏障并进入宿主细胞。在这里，我们表明，肌动蛋白免疫结合蛋白冠调节滑翔运动伯氏疟原虫子孢子，高度能动的形式，啮齿动物疟疾引起的寄生虫传播的蚊子。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，但不会在皮肤中迁移，但会导致传播效率降低。在非运动的子孢子中，低钙浓度介导肌动蛋白非依赖性冠蛋白定位于外周。细胞外配体的参与触发细胞内钙释放，随后是肌动蛋白依赖性的冠状蛋白重新定位到后部并启动运动。突变分析和成像表明，冠状蛋白组织肌动蛋白丝生产性运动。使用冠状蛋白-mCherry作为存在肌动蛋白丝的标记物，我们发现蛋白激酶A有助于肌动蛋白丝的分解。我们最后推测，钙和cAMP介导的信号调节开关从快速寄生虫运动宿主细胞入侵的差异影响肌动蛋白动力学。
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.