Cytoskeletal Components of an Invasion Machine—The Apical Complex of Toxoplasma gondii

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Abstract
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.