title: Trafficking of the major virulence factor to the surface of transfected P. falciparum-infected erythrocytes.
abstract: After invading human red blood cells (RBCs) the malaria parasite Plasmodium falciparum remodels the host cell by trafficking proteins to the RBC compartment. The virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) is responsible for cytoadherence of infected cells to host endothelial receptors. This protein is exported across the parasite plasma membrane and parasitophorous vacuole membrane and inserted into the RBC membrane. We have used green fluorescent protein chimeras and fluorescence photobleaching experiments to follow PfEMP1 export through the infected RBC. Our data show that a knob-associated histidine-rich protein (KAHRP) N-terminal protein export element appended to the PfEMP1 transmembrane and C-terminal domains was sufficient for efficient trafficking of protein domains to the outside of the P. falciparum-infected RBC. The physical state of the exported proteins suggests trafficking as a complex rather than in vesicles and supports the hypothesis that endogenous PfEMP1 is trafficked in a similar manner. This study identifies the sequences required for expression of proteins to the outside of the P. falciparum-infected RBC membrane.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, 3050 Australia.
authors.forename: Ellen
authors.initials: E
authors.lastname: Knuepfer
authors.forename: Melanie
authors.initials: M
authors.lastname: Rug
authors.forename: Nectarios
authors.initials: N
authors.lastname: Klonis
authors.forename: Leann
authors.initials: L
authors.lastname: Tilley
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology* / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D020126:Brefeldin A