Evidence for vesicle-mediated trafficking of parasite proteins to the hostcell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected erythrocytes

Plasmodium falciparum malaria parasites actively remodel the host cell cyto sol and plasma membrane during the erythrocytic cycle. The focus of this in vestigation was to characterize intra-parasitic and -erythrocytic secretory pathways. Electron-dense vesicles, similar in appearance to mammalian secr etory vesicles were detected in proximity to smooth tubo-vesicular elements at the periphery of the parasite cytoplasm in mature parasites by transmis sion electron microscopy. Vesicles (60-100 nm diameter), which appeared to be coated. were visualized on the erythrocytic side of the parasite vacuola r membrane and in the erythrocyte cytosol. The vesicles seemed to bind to a nd Fuse with the erythrocyte membrane, giving rise to cup-shaped electron-d ense structures, which might be intermediates in knob structure formation. Treatment of mature parasites with aluminum tetrafluoride, an activator of GTP-binding proteins, resulted in the accumulation of the vesicles with an electron-dense limiting membrane in the erythrocyte cytosol into multiple v esicle strings. These vesicle complexes were often associated with and clos ely abutted the erythrocyte membrane, but were apparently prevented from fu sing by the aluminum fluoride treatment. The parasite proteins PfEMP1 and P fEMP3 were found by immunoelectron microscopy to be associated with these v esicles. suggesting they are responsible for transporting these proteins to the erythrocyte membrane. (C) 2000 Elsevier Science B.V. All rights reserv ed.