title: Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes.
abstract: After invading human erythrocytes, the malarial parasite Plasmodium falciparum, initiates a remarkable process of secreting proteins into the surrounding erythrocyte cytoplasm and plasma membrane. One of these exported proteins, the knob-associated histidine-rich protein (KAHRP), is essential for microvascular sequestration, a strategy whereby infected red cells adhere via knob structures to capillary walls and thus avoid being eliminated by the spleen. This cytoadherence is an important factor in many of the deaths caused by malaria. Green fluorescent protein fusions and fluorescence recovery after photobleaching were used to follow the pathway of KAHRP deployment from the parasite endomembrane system into an intermediate depot between parasite and host, then onwards to the erythrocyte cytoplasm and eventually into knobs. Sequence elements essential to individual steps in the pathway are defined and we show that parasite-derived structures, known as Maurer's clefts, are an elaboration of the canonical secretory pathway that is transposed outside the parasite into the host cell, the first example of its kind in eukaryotic biology.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne 3050, Australia.
authors.forename: M E
authors.initials: ME
authors.lastname: Wickham
authors.forename: M
authors.initials: M
authors.lastname: Rug
authors.forename: S A
authors.initials: SA
authors.lastname: Ralph
authors.forename: N
authors.initials: N
authors.lastname: Klonis
authors.forename: G I
authors.initials: GI
authors.lastname: McFadden
authors.forename: L
authors.initials: L
authors.lastname: Tilley
authors.forename: A F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D020126:Brefeldin A / Q000494:pharmacology; D002448:Cell Adhesion; D003600:Cytosol / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000187:drug effects; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D010777:Photochemistry; D010963:Plasmodium falciparum / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology
chemical_list: D008164:Luminescent Proteins; D046911:Macromolecular Substances; D010455:Peptides; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C042968:knob protein, Plasmodium falciparum; D049452:Green Fluorescent Proteins; C073415:antigen Pf332, Plasmodium; D020126:Brefeldin A