The high mortality of Plasmodium falciparum malaria is the result of a parasite ligand, PfEMP1 (P. falciparum) erythrocyte membrane protein 1), on the surface of infected red blood cells (IRBCs), which adheres to the vascular endothelium and causes the sequestration of IRBCs in the microvasculature. PfEMP1 transport to the IRBC surface involves Maurer's clefts, which are parasite-derived membranous structures in the IRBC cytoplasm. Targeted gene disruption of a Maurer's cleft protein, SBP1 (skeleton-binding protein 1), prevented IRBC adhesion because of the loss of PfEMP1 expression on the IRBC surface. PfEMP1 was still present in Maurer's clefts, and the transport and localization of several other Maurer's cleft proteins were unchanged. Maurer's clefts were altered in appearance and were no longer found as close to the periphery of the IRBC. Complementation of mutant parasites with sbp1 led to the reappearance of PfEMP1 on the IRBC surface and the restoration of adhesion. Our results demonstrate that SBP1 is essential for the translocation of PfEMP1 onto the surface of IRBCs and is likely to play a pivotal role in the pathogenesis of P. falciparum malaria.
A Maurer's cleft–associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells
Abbreviations used in this paper: FRET, fluorescent resonance energy transfer; hdhfr, human dihydrofolate reductase; HRP, histidine-rich protein; HSP, heat shock protein; IFA, immunofluorescence assay; IRBC, infected RBC; KAHRP, knob-associated HRP; KO, knockout; MAHRP, Maurer's cleft–associated HRP; PEXEL, Plasmodium export element; PfEMP, Plasmodium falciparum erythrocyte membrane protein; REX, ring-stage exported protein; SBP1, skeleton-binding protein 1; VTS, vacuolar transport signal.
Brian M. Cooke, Donna W. Buckingham, Fiona K. Glenister, Kate M. Fernandez, Lawrence H. Bannister, Matthias Marti, Narla Mohandas, Ross L. Coppel; A Maurer's cleft–associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells . J Cell Biol 13 March 2006; 172 (6): 899–908. doi: https://doi.org/10.1083/jcb.200509122
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