Wherever I may roam: Protein and membrane trafficking in P. falciparum-infected red blood cells

P. falciparum is an interesting eukaryotic model system to study protein trafficking. The P. falciparum-infected erythrocyte contains numerous uncommon structures to which proteins must be trafficked. Here we summarize knowledge on this topic. [Display omitted] ► The P. falciparum-infected erythrocyte contains numerous uncommon cellular compartments. ► Proteins must be targeted to these compartments. ► Many of these protein trafficking pathways are only found in P. falciparum-infected cells. ► These trafficking pathways thus show potential as drug targets. Quite aside from its immense importance as a human pathogen, studies in recent years have brought to light the fact that the malaria parasite Plasmodium falciparum is an interesting eukaryotic model system to study protein trafficking. Studying parasite cell biology often reveals an overrepresentation of atypical cell biological features, possibly driven by the parasites’ need to survive in an unusual biological niche. Malaria parasites possess uncommon cellular compartments to which protein traffic must be directed, including secretory organelles such as rhoptries and micronemes, a lysosome-like compartment referred to as the digestive vacuole and a complex (four membrane-bound) plastid, the apicoplast. In addition, the parasite must provide proteins to extracellular compartments and structures including the parasitophorous vacuole, the parasitophorous vacuolar membrane, the Maurer's clefts and both cytosol and plasma membrane of the host cell, the mature human red blood cell. Although some of these unusual destinations are possessed by other cell types, only Plasmodium parasites contain them all within one cell. Here we review what is known about protein and membrane transport in the P. falciparum-infected cell, highlighting novel features of these processes. A growing body of evidence suggests that this parasite is a real “box of tricks” with regards to protein traffic. Possibly, these tricks may be turned against the parasite by exploiting them as novel therapeutic targets.