Protein Sorting in Plasmodium Falciparum

Abstract

Plasmodium falciparum is a unicellular eukaryote with a very polarized secretory system composed of micronemes rhoptries and dense granules that are required for host cell invasion. P. falciparum, like its relative T. gondii, uses the endolysosomal system to produce the secretory organelles and to ingest host cell proteins. The parasite also has an apicoplast, a secondary endosymbiotic organelle, which depends on vesicular trafficking for appropriate incorporation of nuclear-encoded proteins into the apicoplast. Recently, the central molecules responsible for sorting and trafficking in P. falciparum and T. gondii have been characterized. From these studies, it is now evident that P. falciparum has repurposed the molecules of the endosomal system to the secretory pathway. Additionally, the sorting and vesicular trafficking mechanism seem to be conserved among apicomplexans. This review described the most recent findings on the molecular mechanisms of protein sorting and vesicular trafficking in P. falciparum and revealed that P. falciparum has an amazing secretory machinery that has been cleverly modified to its intracellular lifestyle.

Keywords: apicomplexans; endocytic compartment; malaria; protein sorting/trafficking; vesicular trafficking.

Figure 1

Schematic representation of protein trafficking directed by P. falciparum merozoite-infected erythrocyte. The model outlined in this figure is a summary of the recent data on protein sorting and trafficking in P. falciparum and its relative, T. gondii. Secreted proteins are made in the rough ER (RER). Secretory vesicles from the RER are thought to be shipped to the cis-Golgi with the help of SLY1 and Stx5. Bidirectional sorting between the endo-lysosomal compartment (ELC) and the trans-Golgi network (TGN) is also mediated by Vsp45. Transport from the ER to the apicoplast is facilitated by unidentified SNARE proteins. Proteins destined to the micronemes and rhoptries are sorted by the adaptor Stx12. Endocytosis, which leads to the host cell cytosol uptake (HCCU), is likely to occur via the cytostome or the micropore (not shown). These vesicles are shuttled to ELC. The SNARE proteins involved in this process are unknown. Vsp45 is necessary for endocytosis and release of the cargo to the food vacuole. The knobs and some of the proteins involved in PfEMP1 trafficking are shown.