title: Plasmodium falciparumligand binding to erythrocytes induce alterations in deformability essential for invasion.
abstract: The most lethal form of malaria in humans is caused byPlasmodium falciparum. These parasites invade erythrocytes, a complex process involving multiple ligand-receptor interactions. The parasite makes initial contact with the erythrocyte followed by dramatic deformations linked to the function of the Erythrocyte binding antigen family andP. falciparumreticulocyte binding-like families. We show EBA-175 mediates substantial changes in the deformability of erythrocytes by binding to glycophorin A and activating a phosphorylation cascade that includes erythrocyte cytoskeletal proteins resulting in changes in the viscoelastic properties of the host cell. TRPM7 kinase inhibitors FTY720 and waixenicin A block the changes in the deformability of erythrocytes and inhibit merozoite invasion by directly inhibiting the phosphorylation cascade. Therefore, binding ofP. falciparumparasites to the erythrocyte directly activate a signaling pathway through a phosphorylation cascade and this alters the viscoelastic properties of the host membrane conditioning it for successful invasion.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sisquella
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nebl
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Thompson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Whitehead
authors.affiliation: Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St. Louis, United States.|Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, United States.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Malpede
authors.affiliation: Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St. Louis, United States.|Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, United States.
authors.forename: Nichole D
authors.initials: ND
authors.lastname: Salinas
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Kelly
authors.initials: K
authors.lastname: Rogers
authors.affiliation: Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St. Louis, United States.|Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, United States.
authors.forename: Niraj H
authors.identifier: 0000-0002-2689-1337
authors.initials: NH
authors.lastname: Tolia
authors.affiliation: The Queen's Medical Center and John A. Burns School of Medicine, University of Hawaii, Honolulu, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fleig
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Wai-Hong
authors.initials: WH
authors.lastname: Tham
authors.affiliation: Department of Natural Sciences, Hawaii Pacific University, Kaneohe, United States.
authors.forename: F
authors.initials: F
authors.lastname: David Horgen
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Alan F
authors.identifier: 0000-0001-5145-9004
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000953:Antigens, Protozoan / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000502:physiology; D004548:Elasticity; D004705:Endocytosis; D004912:Erythrocytes / Q000166:cytology / Q000469:parasitology* / Q000502:physiology; D006021:Glycophorins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014783:Viscosity
chemical_list: D000953:Antigens, Protozoan; D006021:Glycophorins; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium
keywords: cell biology; erythrocyte; infectious disease; invasion; malaria; merozoite; microbiology