title: Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface.
abstract: A key feature of Plasmodium falciparum, the parasite causing the most severe form of malaria in humans, is its ability to export parasite molecules onto the surface of the erythrocyte. The major virulence factor and variant surface protein PfEMP1 (P falciparum erythrocyte membrane protein 1) acts as a ligand to adhere to endothelial receptors avoiding splenic clearance. Because the erythrocyte is devoid of protein transport machinery, the parasite provides infrastructure for trafficking across membranes it traverses. In this study, we show that the P falciparum skeleton-binding protein 1 (PfSBP1) is required for transport of PfEMP1 to the P falciparum-infected erythrocyte surface. We present evidence that PfSBP1 functions at the parasitophorous vacuole membrane to load PfEMP1 into Maurer clefts during formation of these structures. Furthermore, the major reactivity of antibodies from malaria-exposed multigravid women is directed toward PfEMP1 because this is abolished in the absence of PfSBP1.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Maier
authors.forename: Melanie
authors.initials: M
authors.lastname: Rug
authors.forename: Matthew T
authors.initials: MT
authors.lastname: O'Neill
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.forename: Matthias
authors.initials: M
authors.lastname: Marti
authors.forename: John
authors.initials: J
authors.lastname: Reeder
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002352:Carrier Proteins / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000469:parasitology*; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007425:Intracellular Membranes; D016778:Malaria, Falciparum; D008565:Membrane Proteins / Q000502:physiology*; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: D000913:Antibodies, Protozoan; D002352:Carrier Proteins; D008565:Membrane Proteins; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum