title: The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes.
abstract: Surface protrusions of Plasmodium falciparum-infected erythrocytes, called knobs, display focal aggregates of P falciparum erythrocyte membrane protein 1 (PfEMP1), the adhesion ligand binding endothelial-cell receptors. The resulting sequestration of infected erythrocytes in tissues represents an important factor in the course of fatalities in patients with malaria. The main component of knobs is the knob-associated histidine-rich protein (KAHRP), and it contributes to altered mechanical properties of parasite-infected erythrocytes. The role of KAHRP domains in these processes is still elusive. We generated stable transgenic P falciparum-infected erythrocytes expressing mutant versions of KAHRP. Using atomic force and electron microscopy we show that the C-terminal repeat region is critical for the formation of functional knobs. Elasticity of the membrane differs dramatically between cells with different KAHRP mutations. We propose that the 5' repeat region of KAHRP is important in cross-linking to the host-cell cytoskeleton and this is required for knob protrusion and efficient adhesion under physiologic flow conditions.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Rug
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Prescott
authors.forename: Kate M
authors.initials: KM
authors.lastname: Fernandez
authors.forename: Brian M
authors.initials: BM
authors.lastname: Cooke
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology* / Q000648:ultrastructure; D006801:Humans; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000472:pathogenicity / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D010455:Peptides; D015800:Protozoan Proteins; C042968:knob protein, Plasmodium falciparum