title: Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress.
abstract: 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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: B S
authors.initials: BS
authors.lastname: Crabb
authors.forename: B M
authors.initials: BM
authors.lastname: Cooke
authors.forename: J C
authors.initials: JC
authors.lastname: Reeder
authors.forename: R F
authors.initials: RF
authors.lastname: Waller
authors.forename: S R
authors.initials: SR
authors.lastname: Caruana
authors.forename: K M
authors.initials: KM
authors.lastname: Davern
authors.forename: M E
authors.initials: ME
authors.lastname: Wickham
authors.forename: G V
authors.initials: GV
authors.lastname: Brown
authors.forename: R L
authors.initials: RL
authors.lastname: Coppel
authors.forename: A F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: 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
chemical_list: D001798:Blood Proteins; D018955:CD36 Antigens; D010455:Peptides; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; C042968:knob protein, Plasmodium falciparum