title: Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.
abstract: Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive form of the parasite. None of the few known receptor-ligand interactions involved are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways. Here, we show that we have identified a receptor-ligand pair that is essential for erythrocyte invasion in all tested P. falciparum strains. By systematically screening a library of erythrocyte proteins, we have found that the Ok blood group antigen, basigin, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth. Erythrocyte invasion was potently inhibited by soluble basigin or by basigin knockdown, and invasion could be completely blocked using low concentrations of anti-basigin antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested. Furthermore, Ok(a-) erythrocytes, which express a basigin variant that has a weaker binding affinity for PfRh5, had reduced invasion efficiencies. Our discovery of a cross-strain dependency on a single extracellular receptor-ligand pair for erythrocyte invasion by P. falciparum provides a focus for new anti-malarial therapies.
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
authors.forename: Cécile
authors.initials: C
authors.lastname: Crosnier
authors.forename: Leyla Y
authors.initials: LY
authors.lastname: Bustamante
authors.forename: S Josefin
authors.initials: SJ
authors.lastname: Bartholdson
authors.forename: Amy K
authors.initials: AK
authors.lastname: Bei
authors.forename: Michel
authors.initials: M
authors.lastname: Theron
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchikawa
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Omar
authors.initials: O
authors.lastname: Ndir
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
mesh_terms: D051926:Basigin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D055785:Gene Knockdown Techniques; D006790:Host-Parasite Interactions; D006801:Humans; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000502:physiology*; D017434:Protein Structure, Tertiary
chemical_list: D051926:Basigin
references.citation: Mol Cell Proteomics. 2010 Dec;9(12):2654-65
references.pmid: 20802085
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17327-32
references.pmid: 20855594
references.citation: BMC Biol. 2010 Jun 04;8:76
references.pmid: 20525357
references.citation: Mol Biosyst. 2009 Dec;5(12):1405-12
references.pmid: 19593473
references.citation: Parasitol Today. 1998 Nov;14(11):462-7
references.pmid: 17040849
references.citation: Curr Opin Immunol. 1996 Apr;8(2):257-61
references.pmid: 8725949
references.citation: Genome Biol. 2008;9(12):R171
references.pmid: 19077304
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5348-52
references.pmid: 19279206
references.citation: Genome Res. 2008 Apr;18(4):622-30
references.pmid: 18296487
references.citation: Science. 1994 Jun 24;264(5167):1941-4
references.pmid: 8009226
references.citation: Nature. 2010 Oct 28;467(7319):1061-73
references.pmid: 20981092
references.citation: J Infect Dis. 2010 Dec 1;202(11):1722-7
references.pmid: 20958212
references.citation: PLoS One. 2008 Oct 01;3(10):e3300
references.pmid: 18827878
references.citation: Immunogenetics. 1988;27(5):322-9
references.pmid: 3356449
references.citation: Dev Biol. 1998 Feb 15;194(2):152-65
references.pmid: 9501026
references.citation: Cytometry A. 2010 Nov;77(11):1067-74
references.pmid: 20872885
references.citation: Genome Biol. 2009;10(9):R99
references.pmid: 19765300
references.citation: Nat Rev Genet. 2010 Feb;11(2):149-60
references.pmid: 20084087
references.citation: Cell Host Microbe. 2008 Jul 17;4(1):40-51
references.pmid: 18621009
references.citation: Nature. 2007 Oct 18;449(7164):913-8
references.pmid: 17943131
references.citation: Nat Med. 2003 Jan;9(1):87-92
references.pmid: 12469115
references.citation: Eur J Immunol. 1997 Apr;27(4):891-7
references.pmid: 9130641
references.citation: J Biol Chem. 2008 Jun 27;283(26):18056-65
references.pmid: 18430721
references.citation: Cell. 2006 Feb 24;124(4):755-66
references.pmid: 16497586
references.citation: Mol Microbiol. 2007 Jul;65(2):231-49
references.pmid: 17630968
references.citation: Dev Dyn. 1993 Apr;196(4):252-62
references.pmid: 8219348
references.citation: J Mol Biol. 2009 Aug 21;391(3):518-35
references.pmid: 19500591
references.citation: J Immunogenet. 1990 Aug-Oct;17(4-5):219-25
references.pmid: 2093725
references.citation: Blood. 2006 Aug 1;108(3):791-801
references.pmid: 16861337
references.citation: Nat Genet. 2009 Jun;41(6):657-65
references.pmid: 19465909
references.citation: Int J Parasitol. 2009 Feb;39(3):371-80
references.pmid: 19000690
references.citation: J Biol Chem. 1997 Jan 3;272(1):24-7
references.pmid: 8995219