Erythrocyte invasion by Plasmodium falciparum

Abstract

Malaria poses a severe threat to global public health, with the majority of the world’s population living in malaria-endemic settings. Plasmodium falciparum is a major cause of malaria, and is the predominant cause of fatal malaria. This parasite, like other Plasmodium spp., has a complex life cycle, but causes disease only as a result of a lytic life cycle phase that occurs within the erythrocyte. As development within the erythrocyte is fully responsible for disease pathology, it follows that a detailed molecular understanding of the process of erythrocyte invasion by P. falciparum parasites would allow the development of new and effective therapies. As a step toward such an understanding, we have characterized a complex of proteins that is responsible for driving the process of invasion. This complex was first characterized in Toxoplasma gondii tachyzoites, but is conserved in P. falciparum and consists of four proteins: PfMyoA, PfMTIP, PfGAP45, and PfGAP50. In addition to the general characterization of this complex, we have shown that this complex is a major target of regulation in the P. falciparum merozoite, and that multiple complex members are direct targets of post-translational modification. We have also shown that the post-translational modification of specific members of this complex is dynamic and likely involved in the regulation of complex assembly/disassembly. Finally, we have characterized several broad signaling pathways that are involved in the regulation of erythrocyte invasion.