title: Delivery of the malaria virulence protein PfEMP1 to the erythrocyte surface requires cholesterol-rich domains.
abstract: The particular virulence of the human malaria parasite Plasmodium falciparum derives from export of parasite-encoded proteins to the surface of the mature erythrocytes in which it resides. The mechanisms and machinery for the export of proteins to the erythrocyte membrane are largely unknown. In other eukaryotic cells, cholesterol-rich membrane microdomains or "rafts" have been shown to play an important role in the export of proteins to the cell surface. Our data suggest that depletion of cholesterol from the erythrocyte membrane with methyl-beta-cyclodextrin significantly inhibits the delivery of the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). The trafficking defect appears to lie at the level of transfer of PfEMP1 from parasite-derived membranous structures within the infected erythrocyte cytoplasm, known as the Maurer's clefts, to the erythrocyte membrane. Thus our data suggest that delivery of this key cytoadherence-mediating protein to the host erythrocyte membrane involves insertion of PfEMP1 at cholesterol-rich microdomains. GTP-dependent vesicle budding and fusion events are also involved in many trafficking processes. To determine whether GTP-dependent events are involved in PfEMP1 trafficking, we have incorporated non-membrane-permeating GTP analogs inside resealed erythrocytes. Although these nonhydrolyzable GTP analogs reduced erythrocyte invasion efficiency and partially retarded growth of the intracellular parasite, they appeared to have little direct effect on PfEMP1 trafficking.
authors: Department of Biochemistry, La Trobe University, Melbourne 3086, Australia.
authors: Sarah
authors: S
authors: Frankland
authors: Akinola
authors: A
authors: Adisa
authors: Paul
authors: P
authors: Horrocks
authors: Theodore F
authors: TF
authors: Taraschi
authors: Timothy
authors: T
authors: Schneider
authors: Salenna R
authors: SR
authors: Elliott
authors: Stephen J
authors: SJ
authors: Rogerson
authors: Ellen
authors: E
authors: Knuepfer
authors: Alan F
authors: AF
authors: Cowman
authors: Chris I
authors: CI
authors: Newbold
authors: Leann
authors: L
authors: Tilley