title: Spatial and temporal mapping of the PfEMP1 export pathway in Plasmodium falciparum.
abstract: The human malaria parasite, Plasmodium falciparum, modifies the red blood cells (RBCs) that it infects by exporting proteins to the host cell. One key virulence protein, P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1), is trafficked to the surface of the infected RBC, where it mediates adhesion to the vascular endothelium. We have investigated the organization and development of the exomembrane system that is used for PfEMP1 trafficking. Maurer's cleft cisternae are formed early after invasion and proteins are delivered to these (initially mobile) structures in a temporally staggered and spatially segregated manner. Membrane-Associated Histidine-Rich Protein-2 (MAHRP2)-containing tether-like structures are generated as early as 4 h post invasion and become attached to Maurer's clefts. The tether/Maurer's cleft complex docks onto the RBC membrane at ~20 h post invasion via a process that is not affected by cytochalasin D treatment. We have examined the trafficking of a GFP chimera of PfEMP1 expressed in transfected parasites. PfEMP1B-GFP accumulates near the parasite surface, within membranous structures exhibiting a defined ultrastructure, before being transferred to pre-formed mobile Maurer's clefts. Endogenous PfEMP1 and PfEMP1B-GFP are associated with Electron-Dense Vesicles that may be responsible for trafficking PfEMP1 from the Maurer's clefts to the RBC membrane.
authors: Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Paul J
authors: PJ
authors: McMillan
authors: Coralie
authors: C
authors: Millet
authors: Steven
authors: S
authors: Batinovic
authors: Mauro
authors: M
authors: Maiorca
authors: Eric
authors: E
authors: Hanssen
authors: Shannon
authors: S
authors: Kenny
authors: Rebecca A
authors: RA
authors: Muhle
authors: Martin
authors: M
authors: Melcher
authors: David A
authors: DA
authors: Fidock
authors: Joseph D
authors: JD
authors: Smith
authors: Matthew W A
authors: MW
authors: Dixon
authors: Leann
authors: L
authors: Tilley
mesh_terms: D002478:Cells, Cultured; D004910:Erythrocyte Membrane / Q000469:parasitology / Q000502:physiology; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D049452:Green Fluorescent Proteins; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010963:Plasmodium falciparum / Q000472:pathogenicity* / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D049452:Green Fluorescent Proteins