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. 2006 Mar 13;172(6):899-908. doi: 10.1083/jcb.200509122. Epub 2006 Mar 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism*
  • Carrier Proteins / genetics*
  • Cell Adhesion / genetics
  • Down-Regulation / genetics
  • Erythrocyte Membrane / genetics
  • Erythrocyte Membrane / metabolism
  • Erythrocyte Membrane / ultrastructure
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Erythrocytes / ultrastructure
  • Exocytosis / genetics
  • Gene Expression Regulation / physiology
  • Humans
  • Membrane Proteins / genetics*
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Organelles / metabolism*
  • Organelles / ultrastructure
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / ultrastructure
  • Protein Transport / genetics
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism*


  • Antigens, Surface
  • Carrier Proteins
  • Membrane Proteins
  • Pfsbp1 protein, Plasmodium falciparum
  • Protozoan Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum