An apical protein, Pcr2, is required for persistent movement by the human parasite Toxoplasma gondii.
An apical protein, Pcr2, is required for persistent movement by the human parasite Toxoplasma gondii.
复制标题
DOI：
10.1371/journal.ppat.1010776
复制
发表时间：
2022-08
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
顶复门包括数千种单细胞寄生虫，它们引起广泛的人类和动物疾病，如疟疾和弓形虫病。为了感染，寄生虫必须首先启动主动运动以通过组织传播并侵入宿主细胞，然后一旦进入就停止移动。寄生虫通过在表面上滑行来移动，由内部皮质肌动球蛋白为基础的运动装置推动。在顶复门中最有效的入侵者之一是弓形虫，它可以感染任何有核细胞和任何温血动物。在入侵过程中，寄生虫首先与具有顶端复合体的宿主细胞“正面”接触，顶端复合体具有精细的细胞骨架装置和相关结构。在这里，我们报告的一个新的组成部分的顶端复合物，前锥状区蛋白2（Pcr 2）的鉴定和表征。pcr 2基因敲除的寄生虫可以正常复制，但是它们破坏宿主组织的能力严重降低，这是由于入侵和出口（裂解周期中的两个重要步骤）显著受损。当刺激钙诱导的外出时，Pcr 2敲除寄生虫变得活跃，并分泌效应物以裂解宿主细胞。钙诱导的主要粘附素MIC 2的分泌似乎也是正常的。然而，Pcr 2敲除寄生虫的运动是间歇性的，这极大地损害了出口。除了错误的运动性，Pcr 2敲除寄生虫组装移动连接的能力受损。这两个缺陷都可能导致入侵效率低下。有趣的是，肌动球蛋白的活动，所示的mEmerald标记的肌动蛋白染色体的运动，似乎在很大程度上不受干扰的损失Pcr 2，提高的可能性，Pcr 2可能会采取行动的下游或平行的肌动球蛋白机器。上千种顶复门寄生虫是许多毁灭性的人类和动物疾病的罪魁祸首，包括疟疾和弓形虫病。细胞运动是顶复门寄生虫维持其细胞内寄生生活方式所必需的，它是顶复门寄生虫在组织间传播和侵入宿主细胞所必需的。在这里，我们调查了一个非常成功的apicomplexan，刚地弓形虫的运动。我们发现，前锥状区蛋白2（Pcr 2），一个新的组成部分的寄生虫顶端复合体，是重要的持久性的弓形虫运动。Pcr 2敲除寄生虫的运动是间歇性的，这损害了寄生虫裂解周期中的两个重要步骤--外出和入侵。因此，Pcr 2敲除寄生虫引起的宿主组织破坏要少得多。此外，Pcr 2敲除寄生虫在入侵入口点组装环状结构（移动连接）的能力受损。Pcr 2的发现及其功能的分析为确定与环境的机械相互作用如何影响寄生虫运动，以及寄生虫运动中的持久性的调节或维持如何在功能上与运动装置和参与入侵和出口的其他结构相关联并施加到运动装置和其他结构上提供了新的机会。
The phylum Apicomplexa includes thousands of species of unicellular parasites that cause a wide range of human and animal diseases such as malaria and toxoplasmosis. To infect, the parasite must first initiate active movement to disseminate through tissue and invade into a host cell, and then cease moving once inside. The parasite moves by gliding on a surface, propelled by an internal cortical actomyosin-based motility apparatus. One of the most effective invaders in Apicomplexa is Toxoplasma gondii, which can infect any nucleated cell and any warm-blooded animal. During invasion, the parasite first makes contact with the host cell "head-on" with the apical complex, which features an elaborate cytoskeletal apparatus and associated structures. Here we report the identification and characterization of a new component of the apical complex, Preconoidal region protein 2 (Pcr2). Pcr2 knockout parasites replicate normally, but they are severely diminished in their capacity for host tissue destruction due to significantly impaired invasion and egress, two vital steps in the lytic cycle. When stimulated for calcium-induced egress, Pcr2 knockout parasites become active, and secrete effectors to lyse the host cell. Calcium-induced secretion of the major adhesin, MIC2, also appears to be normal. However, the movement of the Pcr2 knockout parasite is spasmodic, which drastically compromises egress. In addition to faulty motility, the ability of the Pcr2 knockout parasite to assemble the moving junction is impaired. Both defects likely contribute to the poor efficiency of invasion. Interestingly, actomyosin activity, as indicated by the motion of mEmerald tagged actin chromobody, appears to be largely unperturbed by the loss of Pcr2, raising the possibility that Pcr2 may act downstream of or in parallel with the actomyosin machinery. The thousands of species of apicomplexan parasites are responsible for many devastating human and animal diseases, including malaria and toxoplasmosis. Cell movement, needed to disseminate among tissues and invade into a host cell, is essential for the apicomplexan parasites to maintain their intracellular parasitic life style. Here we investigate the movement of a very successful apicomplexan, Toxoplasma gondii. We discovered that Preconoidal region protein 2 (Pcr2), a new component of the parasite apical complex, is important for the persistence of Toxoplasma movement. The movement of the Pcr2 knockout parasite is spasmodic, which compromises egress and invasion, two vital steps in the parasite’s lytic cycle. As a result, Pcr2 knockout parasites cause much less host tissue destruction. Furthermore, the ability of the Pcr2 knockout parasite to assemble a ring-like structure (the moving junction) at the entry point of invasion, is impaired. The discovery of Pcr2 and the analysis of its function open new opportunities to determine how mechanical interactions with its environment impact parasite motility, and how the regulation or maintenance of persistence in parasite movement is functionally connected with and imposed onto the motility apparatus and other structures involved in invasion and egress.
登录
查看更多内容
影响因子：
6.7
作者：
Hu K
通讯作者：
Hu K
弓形虫的裂解周期：15年后。
影响因子：
10.5
作者：
Blader IJ;Coleman BI;Chen CT;Gubbels MJ
通讯作者：
Gubbels MJ
影响因子：
--
作者：
Gras S;Jackson A;Woods S;Pall G;Whitelaw J;Leung JM;Ward GE;Roberts CW;Meissner M
通讯作者：
Meissner M
恶性疟原虫裂殖子中棒状体颈蛋白 RON2 与微线体蛋白 AMA1 形成复合物
影响因子：
1.9
作者：
Cao, Jun;Kaneko, Osamu;Torii, Motomi
通讯作者：
Torii, Motomi
影响因子：
4.8
作者：
Borges-Pereira, Lucas;Budu, Alexandre;Moreno, Silvia N. J.
通讯作者：
Moreno, Silvia N. J.