A Maurer's cleft-associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells.
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.
Cooke
Brian M
BM
Molecular and Cellular Rheology Laboratory, Department of Microbiology, Monash University, Victoria 3800, Australia. brian.cooke@med.monash.edu.au
Buckingham
Donna W
DW
Glenister
Fiona K
FK
Fernandez
Kate M
KM
Bannister
Lawrence H
LH
Marti
Matthias
M
Mohandas
Narla
N
Coppel
Ross L
RL
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004910:Erythrocyte Membrane / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology* / Q000648:ultrastructure; D005089:Exocytosis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D015388:Organelles / Q000378:metabolism* / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*
D000954:Antigens, Surface; D002352:Carrier Proteins; D008565:Membrane Proteins; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum