Transport mechanisms in Plasmodium-infected erythrocytes: lipid rafts and a tubovesicular network.

The mature human erythrocyte is a simple cell that is devoid of intracellular organelles and does not show endocytic or phagocytic activity at the plasma membrane. However, following infection by Plasmodium, the erythrocyte undergoes several morphological and functional changes. Parasite-derived proteins are exported into the erythrocyte cytoplasm and to the membrane, while several proteins are localised to the parasitophorous vacuolar membrane and to the tubovesicular membranous network structures surrounding the parasite. Recent evidence indicates that multiple host proteins, independent of the type of their membrane anchor, that exist in detergent-resistant membrane (DRM) rafts or microdomains enter this apicomplexan vacuole. The internalised host components along with the parasite-encoded transmembrane protein PfEXP1 can be detected as DRM rafts in the vacuole. It appears that in Plasmodium-infected erythrocytes lipid rafts may play a role in endovacuolation and macromolecular transport.

Erythrocytic vacuolar rafts induced by malaria parasites.

Studies in the past year displaced long-standing dogmas and provided many new molecular insights into how proteins and solutes move between the erythrocyte plasma membrane and the malarial vacuole. Highlights include a demonstration that (1) detergent-resistant membrane (DRM) rafts exist in the red cell membrane and their resident proteins are detected as rafts in the plasmodial vacuole, (2) a voltage-gated channel in the infected red cell membrane mediates uptake of extracellular nutrient solutes, and (3) intraerythrocytic membranes transport a parasite-encoded adherence antigen to the red cell surface.

Vacuolar uptake of host components, and a role for cholesterol and sphingomyelin in malarial infection.

Erythrocytes, which are incapable of endocytosis or phagocytosis, can be infected by the malaria parasite Plasmodium falciparum. We find that a transmembrane protein (Duffy), glycosylphosphatidylinositol (GPI)-anchored and cytoplasmic proteins, associated with detergent-resistant membranes (DRMs) that are characteristic of microdomains in host cell membranes, are internalized by vacuolar parasites, while the major integral membrane and cytoskeletal proteins are not. The internalized host proteins and a plasmodial transmembrane resident parasitophorous vacuolar membrane (PVM) protein are detected in DRMs associated with vacuolar parasites. This is the first report of a host transmembrane protein being recruited into an apicomplexan vacuole and of the presence of vacuolar DRMs; it establishes that integral association does not preclude protein internalization into the P.FALCIPARUM: vacuole. Rather, as shown for Duffy, intracellular accumulation occurs at the same rate as that seen for a DRM-associated GPI-anchored protein. Furthermore, novel mechanisms regulated by the DRM lipids, sphingomyelin and cholesterol, mediate (i) the uptake of host DRM proteins and (ii) maintenance of the intracellular vacuole in the non-endocytic red cell, which may have implications for intracellular parasitism and pathogenesis.