Calcium dynamics of Plasmodium berghei sporozoite motility
Calcium dynamics of Plasmodium berghei sporozoite motility
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DOI：
10.1111/cmi.12289
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发表时间：
2014-05-01
影响因子：
3.4
通讯作者：
Amino, Rogerio
中科院分区：
文献类型：
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作者：
Carey, Allison F.;Singer, Mirko;Amino, Rogerio
钙是顶复合体寄生虫的重要信号分子，在包括滑翔运动在内的多种过程中起着重要作用。滑翔对于疟疾寄生虫从皮肤迁移到肝脏以及侵入宿主组织和细胞至关重要。在这里，我们通过实时成像和流式细胞术研究了细胞内Ca2+在伯氏疟原虫孢子体运动中的动态。我们发现，当孢子体在悬浮中被激活时，细胞质内Ca2+水平增加，这足以诱导整合素样粘连素的分泌，这是滑翔运动所必需的。通过离子载体人工增加细胞内Ca2+水平，这些粘附素被分泌到孢子体表面，然而，寄生虫不能滑翔。在与固体底物的附着和脱离过程中观察到第二个水平的Ca2+调节，分别导致细胞质Ca2+水平的进一步增加或减少。我们还观察到在滑行过程中细胞内Ca2+水平的振荡。最后，细胞内Ca2+螯合剂、磷酸肌醇特异性磷脂酶C （PI-PLC）抑制剂和肌醇三磷酸（IP3）受体抑制剂阻断了胞内Ca2+、黏附素分泌和活化孢子子运动的增加，表明胞内储存在孢子子滑动过程中提供Ca2+。我们的研究表明，细胞内Ca2+的增加是必要的，但不足以激活滑行，Ca2+水平在运动过程中以多种方式调节，并且PI-PLC/IP3途径调节孢子运动过程中Ca2+的释放。
Calcium is a key signalling molecule in apicomplexan parasites and plays an important role in diverse processes including gliding motility. Gliding is essential for the malaria parasite to migrate from the skin to the liver as well as to invade host tissues and cells. Here we investigated the dynamics of intracellular Ca2+ in the motility of Plasmodium berghei sporozoites by live imaging and flow cytometry. We found that cytosolic levels of Ca2+ increase when sporozoites are activated in suspension, which is sufficient to induce the secretion of integrin-like adhesins that are essential for gliding motility. By increasing intracellular Ca2+ levels artificially with an ionophore, these adhesins are secreted onto the sporozoite surface, however, the parasite is not capable of gliding. A second level of Ca2+ modulation was observed during attachment to and detachment from a solid substrate, leading to a further increase or a decrease in the cytoplasmic levels of Ca2+ respectively. We also observed oscillations in the intracellular Ca2+ level during gliding. Finally, an intracellular Ca2+ chelator, an inhibitor of phosphoinositide-specific phospholipase C (PI-PLC), and an inhibitor of the inositol triphosphate (IP3) receptor blocked the rise in intracellular Ca2+, adhesin secretion, and motility of activated sporozoites, indicating that intracellular stores supply Ca2+ during sporozoite gliding. Our study indicates that a rise in intracellular Ca2+ is necessary but not sufficient to activate gliding, that Ca2+ levels are modulated in several ways during motility, and that a PI-PLC/IP3 pathway regulates Ca2+ release during the process of sporozoite locomotion.