title: Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton.
abstract: Following invasion of human red blood cells (RBCs) by the malaria parasite, Plasmodium falciparum, a remarkable process of remodeling occurs in the host cell mediated by trafficking of several hundred effector proteins to the RBC compartment. The exported virulence protein, P falciparum erythrocyte membrane protein 1 (PfEMP1), is responsible for cytoadherence of infected cells to host endothelial receptors. Maurer clefts are organelles essential for protein trafficking, sorting, and assembly of protein complexes. Here we demonstrate that disruption of PfEMP1 trafficking protein 1 (PfPTP1) function leads to severe alterations in the architecture of Maurer's clefts. Furthermore, 2 major surface antigen families, PfEMP1 and STEVOR, are no longer displayed on the host cell surface leading to ablation of cytoadherence to host receptors. PfPTP1 functions in a large complex of proteins and is required for linking of Maurer's clefts to the host actin cytoskeleton.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;
authors.forename: Melanie
authors.initials: M
authors.lastname: Rug
authors.affiliation: Department of Infectious Diseases-Parasitology, University of Heidelberg, Heidelberg, Germany;
authors.forename: Marek
authors.initials: M
authors.lastname: Cyrklaff
authors.affiliation: Research School of Biology, The Australian National University, Canberra, Australia;
authors.forename: Antti
authors.initials: A
authors.lastname: Mikkonen
authors.affiliation: Department of Infectious Diseases-Parasitology, University of Heidelberg, Heidelberg, Germany;
authors.forename: Leandro
authors.initials: L
authors.lastname: Lemgruber
authors.affiliation: Research School of Biology, The Australian National University, Canberra, Australia;
authors.forename: Simone
authors.initials: S
authors.lastname: Kuelzer
authors.affiliation: Department of Infectious Diseases-Parasitology, University of Heidelberg, Heidelberg, Germany;
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Sanchez
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thompson
authors.affiliation: Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Hanssen
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;
authors.forename: Matthew
authors.initials: M
authors.lastname: O'Neill
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;
authors.forename: Christine
authors.initials: C
authors.lastname: Langer
authors.affiliation: Department of Infectious Diseases-Parasitology, University of Heidelberg, Heidelberg, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Lanzer
authors.affiliation: Department of Infectious Diseases-Parasitology, University of Heidelberg, Heidelberg, Germany;
authors.forename: Friedrich
authors.initials: F
authors.lastname: Frischknecht
authors.affiliation: Research School of Biology, The Australian National University, Canberra, Australia;
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Maier
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000953:Antigens, Protozoan / Q000378:metabolism*; D002478:Cells, Cultured; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism / Q000469:parasitology; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000199:Actins; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C474556:STEVOR antigen, Plasmodium falciparum; D037521:Virulence Factors; C085731:erythrocyte membrane protein 1, Plasmodium falciparum