The cytoplasmic domain of the Plasmodium falciparum ligand EBA-175 is essential for invasion but not protein trafficking.
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.
Gilberger
Tim-Wolf
TW
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
Thompson
Jennifer K
JK
Reed
Michael B
MB
Good
Robert T
RT
Cowman
Alan F
AF
D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000737:chemistry; D000818:Animals; D030801:Animals, Genetically Modified; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017124:Conserved Sequence; D003593:Cytoplasm / Q000737:chemistry* / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D024342:Amino Acids, Acidic; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D006021:Glycophorins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium; C069428:thrombospondin-related adhesive protein, protozoan; D014443:Tyrosine