BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum

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 in...

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Main Authors:	Crosnier, Cécile, Bustamante, Leyla Y., Bartholdson, S. Josefin, Bei, Amy K., Theron, Michel, Uchikawa, Makoto, Mboup, Souleymane, Ndir, Omar, Kwiatkowski, Dominic P., Duraisingh, Manoj T., Rayner, Julian C., Wright, Gavin J.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245779/

id	pubmed-3245779
recordtype	oai_dc
spelling	pubmed-32457792012-06-22 BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum Crosnier, Cécile Bustamante, Leyla Y. Bartholdson, S. Josefin Bei, Amy K. Theron, Michel Uchikawa, Makoto Mboup, Souleymane Ndir, Omar Kwiatkowski, Dominic P. Duraisingh, Manoj T. Rayner, Julian C. Wright, Gavin J. Article 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 involved1-4 are required in all parasite strains suggesting that the parasite is able to access multiple redundant invasion pathways5. 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 growth6. 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, exhibited 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 novel anti-malarial therapies. 2011-11-09 /pmc/articles/PMC3245779/ /pubmed/22080952 http://dx.doi.org/10.1038/nature10606 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Crosnier, Cécile Bustamante, Leyla Y. Bartholdson, S. Josefin Bei, Amy K. Theron, Michel Uchikawa, Makoto Mboup, Souleymane Ndir, Omar Kwiatkowski, Dominic P. Duraisingh, Manoj T. Rayner, Julian C. Wright, Gavin J.
spellingShingle	Crosnier, Cécile Bustamante, Leyla Y. Bartholdson, S. Josefin Bei, Amy K. Theron, Michel Uchikawa, Makoto Mboup, Souleymane Ndir, Omar Kwiatkowski, Dominic P. Duraisingh, Manoj T. Rayner, Julian C. Wright, Gavin J. BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum
author_facet	Crosnier, Cécile Bustamante, Leyla Y. Bartholdson, S. Josefin Bei, Amy K. Theron, Michel Uchikawa, Makoto Mboup, Souleymane Ndir, Omar Kwiatkowski, Dominic P. Duraisingh, Manoj T. Rayner, Julian C. Wright, Gavin J.
author_sort	Crosnier, Cécile
title	BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum
title_short	BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum
title_full	BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum
title_fullStr	BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum
title_full_unstemmed	BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum
title_sort	basigin is a receptor essential for erythrocyte invasion by plasmodium falciparum
description	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 involved1-4 are required in all parasite strains suggesting that the parasite is able to access multiple redundant invasion pathways5. 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 growth6. 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, exhibited 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 novel anti-malarial therapies.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245779/
_version_	1611496482084487168

BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum

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