Functional alteration of red blood cells by a megadalton protein of Plasmodium falciparum

Proteins exported from Plasmodium falciparum parasites into red blood cells (RBCs) interact with the membrane skeleton and contribute to the pathogenesis of malaria. Specifically, exported proteins increase RBC membrane rigidity, decrease deformability, and increase adhesiveness, culminating in intr...

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Bibliographic Details
Published in:Blood 2009-01, Vol.113 (4), p.919-928
Main Authors: Glenister, Fiona K., Fernandez, Kate M., Kats, Lev M., Hanssen, Eric, Mohandas, Narla, Coppel, Ross L., Cooke, Brian M.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Adhesion
Cells, Cultured
Erythrocytes - cytology
Erythrocytes - metabolism
Gene Deletion
Gene Expression Regulation
Human protozoal diseases
Humans
Infectious diseases
Malaria
Medical sciences
Microscopy, Electron, Transmission
Molecular Weight
Mutation - genetics
Parasitic diseases
Plasmodium falciparum - genetics
Plasmodium falciparum - metabolism
Plasmodium falciparum - ultrastructure
Protein Transport
Protozoal diseases
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Red Cells, Iron, and Erythropoiesis
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Summary:Proteins exported from Plasmodium falciparum parasites into red blood cells (RBCs) interact with the membrane skeleton and contribute to the pathogenesis of malaria. Specifically, exported proteins increase RBC membrane rigidity, decrease deformability, and increase adhesiveness, culminating in intravascular sequestration of infected RBCs (iRBCs). Pf332 is the largest (>1 MDa) known malaria protein exported to the RBC membrane, but its function has not previously been determined. To determine the role of Pf332 in iRBCs, we have engineered and analyzed transgenic parasites with Pf332 either deleted or truncated. Compared with RBCs infected with wild-type parasites, mutants lacking Pf332 were more rigid, were significantly less adhesive to CD36, and showed decreased expression of the major cytoadherence ligand, PfEMP1, on the iRBC surface. These abnormalities were associated with dramatic morphologic changes in Maurer clefts (MCs), which are membrane structures that transport malaria proteins to the RBC membrane. In contrast, RBCs infected with parasites expressing truncated forms of Pf332, although still hyperrigid, showed a normal adhesion profile and morphologically normal MCs. Our results suggest that Pf332 both modulates the level of increased RBC rigidity induced by P falciparum and plays a significant role in adhesion by assisting transport of PfEMP1 to the iRBC surface.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-05-157735