Cytoskeletal components of an invasion machine--the apical complex of Toxoplasma gondii.

The apical complex of Toxoplasma gondii is widely believed to serve essential functions in both invasion of its host cells (including human cells), and in replication of the parasite. The understanding of apical complex function, the basis for its novel structure, and the mechanism for its motility are greatly impeded by lack of knowledge of its molecular composition. We have partially purified the conoid/apical complex, identified ~200 proteins that represent 70% of its cytoskeletal protein components, characterized seven novel proteins, and determined the sequence of recruitment of five of these proteins into the cytoskeleton during cell division. Our results provide new markers for the different subcompartments within the apical complex, and revealed previously unknown cellular compartments, which facilitate our understanding of how the invasion machinery is built. Surprisingly, the extreme apical and extreme basal structures of this highly polarized cell originate in the same location and at the same time very early during parasite replication. Toxoplasma gondii, the leading cause of human congenital neurological defects, is also closely related to the malaria parasite Plasmodium falciparum. To survive and multiply, these parasites must invade a host cell. Once inside the cell, the parasites quickly outgrow their host and then break out, destroying the host cell in the process. The damage they cause is almost entirely due to uncontrolled cycles of host-cell invasion, parasite multiplication, and host-cell destruction. Both the invasion of host cells and parasite multiplication seem to rely on a remarkable set of structures known as the apical complex. The authors thought that a better understanding of how the apical complex does its job might lead to new ideas for combating diseases caused by this family of parasites. Unfortunately, the molecular components of the apical complex were unknown, which severely hampered study of its function. Hu et al. developed a procedure for identifying most of the proteins used to build the apical complex, and report the results in this paper. The work provides the basis for future studies of how these proteins work, and thus ultimately a basis for choosing targets against which more effective drugs could be designed.

刚地弓形虫的顶复体被广泛认为在其入侵宿主细胞（包括人类细胞）以及寄生虫的复制过程中都起着关键作用。由于对其分子组成缺乏了解，对顶复体功能的理解、其独特结构的基础以及其运动机制都受到了极大的阻碍。我们已经部分纯化了锥体/顶复体，鉴定出约200种蛋白质，这些蛋白质占其细胞骨架蛋白成分的70%，对7种新蛋白质进行了特性分析，并确定了在细胞分裂过程中其中5种蛋白质被招募到细胞骨架中的顺序。我们的研究结果为顶复体内部不同的亚区室提供了新的标记，并揭示了以前未知的细胞区室，这有助于我们理解入侵机制是如何构建的。令人惊讶的是，这种高度极化细胞的顶端和基端结构在寄生虫复制的极早期源自同一位置且同时产生。 刚地弓形虫是人类先天性神经缺陷的主要病因，它也与疟原虫恶性疟原虫密切相关。为了生存和繁殖，这些寄生虫必须入侵宿主细胞。一旦进入细胞内，寄生虫会迅速生长超过其宿主，然后突破出来，在此过程中破坏宿主细胞。它们造成的损害几乎完全是由于宿主细胞入侵、寄生虫繁殖和宿主细胞破坏的不受控制的循环。宿主细胞的入侵和寄生虫的繁殖似乎都依赖于一组被称为顶复体的显著结构。作者们认为，更好地理解顶复体如何发挥作用可能会为对抗这一类寄生虫引起的疾病带来新的思路。 不幸的是，顶复体的分子成分是未知的，这严重阻碍了对其功能的研究。胡等人开发了一种鉴定用于构建顶复体的大多数蛋白质的方法，并在本文中报告了结果。这项工作为未来研究这些蛋白质如何发挥作用提供了基础，从而最终为选择可以针对其设计更有效药物的靶点提供了基础。