Common trafficking pathway for variant antigens destined for the surface of the Plasmodium falciparum-infected erythrocyte.
Intraerythrocytic Plasmodium falciparum exports proteins to the cytosol and to the plasma membrane of the host cell. We here present data revealing the existence of a unique common pathway for the surface bound traffic of the clonally variant antigens, repeated-interspersed-antigen (RIFINS) and P. falciparum erythrocyte-membrane-protein-1 (PfEMP1). RIFIN- and PfEMP1-specific antibodies were found to stain single small vesicles (SSV) that bud off from the parasitophorus vacuolar membrane (PMV) at 6-10 h post-invasion. Large multimeric vesicle (LMV) assemblies, composed of subunits each of a similar size to that of a SSV, appeared as the dominant vesicle type carrying the variant antigens in the cytosol as the parasites developed into early trophozoite stages (> or = 16 h post-invasion). Later, more than 24 h post-invasion, large spinle-like vesicles (LSLV) built up as the LMV approached and accumulated underneath the erythrocyte membrane. LMV were found to associate both with the Maurer's cleft antigen Pf332 and with lipids as seen by fluorescent BODIPY-Ceramide staining. Co-traffic of Pf332 with RIFINS and PfEMP1 occurred in sub-compartmentalized LMV, as the variant antigens co-localized at the outer rim while Pf332 occupied the core of the vesicle complex. Formation of LMV for the trafficking of RIFINS and PfEMP1 is a prominent feature of freshly isolated P. falciparum and of in vitro propagated K+ as well as K- parasites, seemingly independent of the knob-associated histidine-rich protein (KAHRP). In vitro cultured 3D7 clones lack LMV formation and traffic the variant antigens in vesicles of a similar size to that of the SSV.
Haeggström
Malin
M
Microbiology and Tumorbiology Center, Karolinska Institutet, Nobels väg 16, Box 280, SE-171 77 Stockholm, Sweden.
Kironde
Fred
F
Berzins
Klavs
K
Chen
Qijun
Q
Wahlgren
Mats
M
Fernandez
Victor
V
D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*
D000953:Antigens, Protozoan; C044243:FIRA protein, Plasmodium falciparum; D008565:Membrane Proteins; D010455:Peptides; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; C042968:knob protein, Plasmodium falciparum; C073415:antigen Pf332, Plasmodium