Investigations into the Nature of the Endosomal System in Plasmodium falciparum
Krai, Priscilla M.
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The parasite Plasmodium falciparum causes the most virulent form of human malaria and is responsible for the vast majority of malaria-related deaths. During the asexual intraerythrocytic stage, the parasite must transport newly synthesized proteins and endocytosed cargo to a variety of organelles, many of which are formed de novo and have no human equivalent. This process in mammalian cells would utilize an endosomal protein trafficking system, but no endosomal structures or proteins have been described in the parasite. Prior work on the parasite genome indicated that several proteins, which could potentially coordinate an endosomal network, were encoded in the genome and expressed during the asexual parasite stages. In this study, we have localized and attempted to further characterize these proteins in the context of the endosomal system. Two well-conserved protein components of the late endosome, the retromer cargo-selective complex and Rab7, were found on a previously un-described inherited structure adjacent to the parasite Golgi apparatus and in close opposition to nascent rhoptries (specialized secretory organelles required for invasion). The retromer cargo-selective complex was also in close proximity to its putative cargo, a P. falciparum homolog of the sortilin family of protein sorting receptors, PfSortilin. Another protein, PfFCP, the sole FYVE domain-containing protein in the P. falciparum genome, was localized to the membrane of a specialized acidic organelle, known as the food vacuole, where the parasite catabolizes the majority of its host cell hemoglobin. We analyzed the effects of a PfFCP dominant negative mutant and found that it altered food vacuole morphology and trafficking. A previous report localized the early endosome phosphoinositide, phosphatidylinositol 3-phosphate, to the food vacuole membrane, and in conjunction with our studies on PfFCP, this has raised doubts about the food vacuole as a lysosome equivalent in the parasite. The combination of both early and late endosome protein homologs in the parasite, and their potential function, has led to a new model of protein trafficking within the parasite that includes the food vacuole as a terminal early endosome and the apical organelles as lysosome equivalents.
- Doctoral Dissertations