Model of lipid and protein uptake into the erythrocyte DIV (indicates drug-induced vesicle) and the malarial vacuole. (A) The erythrocyte membrane contains a variety of phospholipids (PS, PI/PIP2, PE, PG, etc) and raft (stomatin, flotillins) and nonraft (actin, spectrin) proteins, most of which are taken up into DIV membranes. However, PE- and PG-type phospholipids are specifically excluded from these DIVs. Triangles represent membrane raft proteins flotillin-1 and flotillin-2 (light blue) and stomatin (black). Red bars and blue curved bars represent cytoskeletal actin and spectrin, respectively. Circles represent phospholipids PS (purple), PIP2 (green), PE (yellow), or PG (black). (B) Model of lipid and protein uptake into the malarial vacuolar membrane. Although the merozoite-induced indentation of the nascent vacuole may be remarkably similar to that of DIVs, the fully formed vacuole appears specifically enriched in flotillins, some additional raft proteins (not shown), and host PS. Unlike DIVs, the malarial vacuolar membrane is devoid of cytoskeleton, PIP2, and membrane raft stomatin; arrows depict the selective departure of actin, PIP2, stomatin, and spectrin from the forming malarial vacuole. This selectivity may reflect the combined contribution of erythrocyte-dependent molecular sorting on the basis of membrane curvature and lipid composition as well as potential contributions from parasite-encoded factors that serve to modify the vacuolar membrane during malarial invasion. PE and PG are not shown in panel B. In panel A, a flippase activity is implicated to keep PS cytoplasmically oriented in erythrocytes and DIVs. In malarial invasion (panel B), PS is not exposed at the infected erythrocyte membrane during PVM formation; it remains unknown whether PS is lumenal in the PVM. Our result that PS is detected on the cytoplasmic face of the vacuole is the first clear evidence of PS distribution in the PVM. Murphy SC, Fernandez-Pol S, Chung PH, Prasanna Murthy SN, Milne SB, Salomao M, Brown HA, Lomasney JW, Mohandas N, Haldar K. Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human malaria parasite Plasmodium falciparum. Blood. 2007 110(6):2132-9. PMID: 17526861