Super-Resolution Dissection of Coordinated Events during Malaria Parasite Invasion of the Human Erythrocyte
Super-Resolution Dissection of Coordinated Events during Malaria Parasite Invasion of the Human Erythrocyte
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DOI：
10.1016/j.chom.2010.12.003
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发表时间：
2011-01-20
影响因子：
30.3
通讯作者：
Baum, Jake
中科院分区：
文献类型：
--
作者：
Riglar, David T.;Richard, Dave;Baum, Jake
裂殖子侵入红细胞是疟原虫感染的必经阶段，也是疟疾疾病进展的关键。研究这一过程的尝试受到了来自唯一体外培养适应的人类疟疾寄生虫恶性疟原虫的裂殖子的入侵同步性差的阻碍。使用荧光，三维结构照明，和免疫电子显微镜过滤裂殖子，我们分析细胞和分子事件的基础上的每个离散步骤的入侵。监测这些事件的动态显示，该过程的承诺是通过裂殖子附着到红细胞介导的，触发所有随后的入侵事件，然后在没有明显检查点的情况下进行。相反，入侵过程的协调涉及裂殖子-红细胞紧密连接的形成，其充当棒状体分泌、表面蛋白脱落和肌动球蛋白马达激活的联系。分解每个分子步骤的能力使我们能够为寄生虫入侵的分子基础提出一个全面的模型。
Erythrocyte invasion by the merozoite is an obligatory stage in Plasmodium parasite infection and essential to malaria disease progression. Attempts to study this process have been hindered by the poor invasion synchrony of merozoites from the only in vitro culture-adapted human malaria parasite, Plasmodium falciparum. Using fluorescence, three-dimensional structured illumination, and immunoelectron microscopy of filtered merozoites, we analyze cellular and molecular events underlying each discrete step of invasion. Monitoring the dynamics of these events revealed that commitment to the process is mediated through merozoite attachment to the erythrocyte, triggering all subsequent invasion events, which then proceed without obvious checkpoints. Instead, coordination of the invasion process involves formation of the merozoite-erythrocyte tight junction, which acts as a nexus for rhoptry secretion, surface-protein shedding, and actomyosin motor activation. The ability to break down each molecular step allows us to propose a comprehensive model for the molecular basis of parasite invasion.