The roles of Centrin 2 and Dynein Light Chain 8a in apical secretory organelles discharge of Toxoplasma gondii
The roles of Centrin 2 and Dynein Light Chain 8a in apical secretory organelles discharge of Toxoplasma gondii
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DOI：
10.1111/tra.12673
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发表时间：
2019-08-01
期刊：
影响因子：
4.5
通讯作者：
Frenal, Karine
中科院分区：
文献类型：
--
作者：
Lentini, Gaelle;Dubois, David J.;Frenal, Karine
为了有效地进入宿主细胞，弓形虫等顶端复合体寄生虫依赖于由基于微管蛋白的结构以及两组称为微线体和棒状体的分泌细胞器组成的顶端复合体。这些细胞器的运输和对接到寄生虫的顶端对于其内容物的排出至关重要。在这里，我们描述了两种通常与微管相关的蛋白质：中心蛋白 2 (CEN2) 和动力蛋白轻链 8a (DLC8a)，它们是有效宿主细胞侵袭所必需的。 CEN2 定位于四个不同的区室，值得注意的是，蛋白质的条件性消耗以逐步的方式发生，依次消耗每个位置的蛋白质库。这一现象使我们能够辨别 CEN2 顶端池对于微线体分泌、运动、入侵和流出的基本功能。 DLC8a 定位于锥状体，除了棒状体细胞器的顶端对接之外，其耗尽还会扰乱微线体的胞吐作用，从而导致宿主细胞侵袭的严重缺陷。 CEN2 和 DLC8a 的表型特征表明，虽然这两种蛋白都参与微线体分泌，但它们可能在导致细胞器胞吐作用的级联事件中的不同步骤发挥作用。
To efficiently enter host cells, apicomplexan parasites such as Toxoplasma gondii rely on an apical complex composed of tubulin-based structures as well as two sets of secretory organelles named micronemes and rhoptries. The trafficking and docking of these organelles to the apical pole of the parasite is crucial for the discharge of their contents. Here, we describe two proteins typically associated with microtubules, Centrin 2 (CEN2) and Dynein Light Chain 8a (DLC8a), that are required for efficient host cell invasion. CEN2 localizes to four different compartments, and remarkably, conditional depletion of the protein occurs in stepwise manner, sequentially depleting the protein pools from each location. This phenomenon allowed us to discern the essential function of the apical pool of CEN2 for microneme secretion, motility, invasion and egress. DLC8a localizes to the conoid, and its depletion also perturbs microneme exocytosis in addition to the apical docking of the rhoptry organelles, causing a severe defect in host cell invasion. Phenotypic characterization of CEN2 and DLC8a indicates that while both proteins participate in microneme secretion, they likely act at different steps along the cascade of events leading to organelle exocytosis.