The cytoplasmic domain of the Plasmodium falciparum ligand EBA-175 is essential for invasion but not protein trafficking

J Cell Biol. 2003 Jul 21;162(2):317-27. doi: 10.1083/jcb.200301046.

Abstract

The invasion of host cells by the malaria parasite Plasmodium falciparum requires specific protein-protein interactions between parasite and host receptors and an intracellular translocation machinery to power the process. The transmembrane erythrocyte binding protein-175 (EBA-175) and thrombospondin-related anonymous protein (TRAP) play central roles in this process. EBA-175 binds to glycophorin A on human erythrocytes during the invasion process, linking the parasite to the surface of the host cell. In this report, we show that the cytoplasmic domain of EBA-175 encodes crucial information for its role in merozoite invasion, and that trafficking of this protein is independent of this domain. Further, we show that the cytoplasmic domain of TRAP, a protein that is not expressed in merozoites but is essential for invasion of liver cells by the sporozoite stage, can substitute for the cytoplasmic domain of EBA-175. These results show that the parasite uses the same components of its cellular machinery for invasion regardless of the host cell type and invasive form.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids, Acidic / chemistry
  • Animals
  • Animals, Genetically Modified
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Conserved Sequence
  • Cytoplasm / chemistry*
  • Cytoplasm / parasitology
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology
  • Glycophorins / metabolism
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / pathogenicity*
  • Protein Transport*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Tyrosine / chemistry

Substances

  • Amino Acids, Acidic
  • Antigens, Protozoan
  • Carrier Proteins
  • Glycophorins
  • Protozoan Proteins
  • Recombinant Proteins
  • erythrocyte-binding antigen 175, Plasmodium
  • thrombospondin-related adhesive protein, protozoan
  • Tyrosine