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Targeted mutagenesis of Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) disrupts cytoadherence of malaria‐infected red blood cells
Author(s) -
Waterkeyn Jacqueline G.,
Wickham Mark E.,
Davern Kathleen M.,
Cooke Brian M.,
Coppel Ross L.,
Reeder John C.,
Culvenor Janetta G.,
Waller Ross F.,
Cowman Alan F.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.12.2813
Subject(s) - biology , plasmodium falciparum , red blood cell , malaria , virology , erythrocyte membrane , band 3 , blood cell , membrane protein , plasmodium (life cycle) , mutagenesis , immunology , microbiology and biotechnology , biochemistry , mutation , parasite hosting , membrane , gene , world wide web , computer science
Adhesion of parasite‐infected red blood cells to the vascular endothelium is a critical event in the pathogenesis of malaria caused by Plasmodium falciparum . Adherence is mediated by the variant erythrocyte membrane protein 1 (PfEMP1). Another protein, erythrocyte membrane protein‐3 (PfEMP3), is deposited under the membrane of the parasite‐infected erythrocyte but its function is unknown. Here we show that mutation of PfEMP3 disrupts transfer of PfEMP1 to the outside of the P.falciparum ‐infected cell. Truncation of the C‐terminal end of PfEMP3 by transfection prevents distribution of this large (>300 kDa) protein around the membrane but does not disrupt trafficking of the protein from the parasite to the cytoplasmic face of the erythrocyte membrane. The truncated PfEMP3 accumulates in structures that appear to be associated with the erythrocyte membrane. We show that accumulation of mutated PfEMP3 blocks the transfer of PfEMP1 onto the outside of the parasitized cell surface and suggest that these proteins traffic through an erythrocyte membrane‐associated compartment that is involved in the transfer of PfEMP1 to the surface of the parasite‐infected red blood cell.