Abstract
The virulence of Plasmodium falciparum relates in part to the cytoadhesion characteristics of parasitized erythrocytes but the molecular basis of the different qualitative and quantitative binding phenotypes is incompletely understood. This paucity of information is due partly to the difficulty in working with membrane proteins, the variant nature of these surface antigens and their relatively low abundance. To address this two-dimensional (2D) protein profiles of closely related, but phenotypically different laboratory strains of P. falciparum have been characterized using proteomic approaches. Since the mature erythrocyte has no nucleus and no protein synthesis capability, metabolic labelling of proteins was used to selectively identify parasite proteins and increase detection sensitivity.A small number of changes (less than 10) were observed between four different P. falciparum laboratory strains with distinctive cytoadherence properties using metabolic labelling, with more parasite protein changes found in trophozoite iRBCs than ring stage. The combination of metabolic labelling and autoradiography can therefore be used to identify parasite protein differences, including quantitative ones, and in some cases to obtain protein identifications by mass spectrometry. The results support the suggestion that the membrane protein profile may be related to cytoadherent properties of the iRBCs. Most changes between parasite variants were differences in iso-electric point indicating differential protein modification rather than the presence or absence of a specific peptide.
Highlights
The virulence of the human malaria parasite Plasmodium falciparum is believed to relate in part to adhesion of parasitized erythrocytes to postcapillary venular endothelium and other uninfected blood cells
Surface antigens from infected erythrocytes interact with several host receptors such as CD36 [1,2,3], Intercellular adhesion molecule-1 (ICAM-1) (CD54) [4], thrombospondin [5], E-selectin (CD62E), vascular cell adhesion molecule VCAM-1 (CD106) [6], P-selectin (CD62P) [7], αvβ3-integrin [8], platelet endothelial cell adhesion molecule-1 [PECAM-1 (CD31)] [9], Chondroitin sulfate A (CSA) [10], Complement receptor-1 (CR-1)),(CD35) [11], Heparan sulphate (HS)-like Glycosaminoglycan (GAG) [12], ABO blood group antigens [13] resulting in the rosetting, agglutination [14] and cytoadherence of
A parasite-derived adhesion molecule that mediates these interactions has been identified as P. falciparum erythrocyte membrane protein 1 (PfEMP1), which is encoded by the var multigene family [15,16,17]
Summary
The virulence of the human malaria parasite Plasmodium falciparum is believed to relate in part to adhesion of parasitized erythrocytes to postcapillary venular endothelium and other uninfected blood cells. A number of other parasite proteins associated with the erythrocyte membrane and exported on the surface of parasitized erythrocytes have been reported, including, Rifin, Stevor, ring surface protein (RSP) 1/2, (for a review see [20]) and, more recently, Surfins [21]. These proteins form part of a group of P. falciparum proteins that contain signals for export from the parasitophorous vacuole [22,23]. Further bioinformatic analysis has proposed over 200 proteins that contain these signals and this behaviour appears to have been adopted much more extensively in P. falciparum than in other Plasmodium species [24], perhaps in part due to its requirement to undergo antigenic variation and cytoadherence
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