title: Analyses of interactions between heparin and the apical surface proteins of Plasmodium falciparum.
abstract: Heparin, a sulfated glycoconjugate, reportedly inhibits the blood-stage growth of the malaria parasite Plasmodium falciparum. Elucidation of the inhibitory mechanism is valuable for developing novel invasion-blocking treatments based on heparin. Merozoite surface protein 1 has been reported as a candidate target of heparin; however, to better understand the molecular mechanisms involved, we characterized the molecules that bind to heparin during merozoite invasion. Here, we show that heparin binds only at the apical tip of the merozoite surface and that multiple heparin-binding proteins localize preferentially in the apical organelles. To identify heparin-binding proteins, parasite proteins were fractionated by means of heparin affinity chromatography and subjected to immunoblot analysis with ligand-specific antibodies. All tested members of the Duffy and reticulocyte binding-like families bound to heparin with diverse affinities. These findings suggest that heparin masks the apical surface of merozoites and blocks interaction with the erythrocyte membrane after initial attachment.
authors.affiliation: 1] Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, the University of Tokyo [2] Division of Stem Cell Processing, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, the University of Tokyo [3] Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, the University of Tokyo.
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Takano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takemae
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Sugi
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishiwa
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gong
authors.forename: Frances C
authors.initials: FC
authors.lastname: Recuenco
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Akashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kato
mesh_terms: D000953:Antigens, Protozoan / Q000737:chemistry / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D006493:Heparin; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases