Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress.
Knobs at the surface of erythrocytes infected with Plasmodium falciparum have been proposed to be important in adherence of these cells to the vascular endothelium. This structure contains the knob-associated histidine-rich protein (KAHRP) and the adhesion receptor P. falciparum erythrocyte membrane protein 1. We have disrupted the gene encoding KAHRP and show that it is essential for knob formation. Knob-transfectants adhere to CD36 in static assays; when tested under flow conditions that mimic those of postcapillary venules, however, the binding to CD36 was dramatically reduced. These data suggest that knobs on P. falciparum-infected erythrocytes exert an important influence on adherence of parasitized-erythrocytes to microvascular endothelium, an important process in the pathogenesis of P. falciparum infections.
Crabb
B S
BS
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Cooke
B M
BM
Reeder
J C
JC
Waller
R F
RF
Caruana
S R
SR
Davern
K M
KM
Wickham
M E
ME
Brown
G V
GV
Coppel
R L
RL
Cowman
A F
AF
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000648:ultrastructure; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology*; D015870:Gene Expression; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000032:analysis; D013314:Stress, Mechanical; D014162:Transfection
D001798:Blood Proteins; D018955:CD36 Antigens; D010455:Peptides; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; C042968:knob protein, Plasmodium falciparum