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A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention tar...

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Autores principales: Yiangou, Loukia, Montandon, Ruddy, Modrzynska, Katarzyna, Rosen, Barry, Bushell, Wendy, Hale, Christine, Billker, Oliver, Rayner, Julian C., Pance, Alena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928779/
https://www.ncbi.nlm.nih.gov/pubmed/27362409
http://dx.doi.org/10.1371/journal.pone.0158238
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author Yiangou, Loukia
Montandon, Ruddy
Modrzynska, Katarzyna
Rosen, Barry
Bushell, Wendy
Hale, Christine
Billker, Oliver
Rayner, Julian C.
Pance, Alena
author_facet Yiangou, Loukia
Montandon, Ruddy
Modrzynska, Katarzyna
Rosen, Barry
Bushell, Wendy
Hale, Christine
Billker, Oliver
Rayner, Julian C.
Pance, Alena
author_sort Yiangou, Loukia
collection PubMed
description The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.
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spelling pubmed-49287792016-07-18 A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei Yiangou, Loukia Montandon, Ruddy Modrzynska, Katarzyna Rosen, Barry Bushell, Wendy Hale, Christine Billker, Oliver Rayner, Julian C. Pance, Alena PLoS One Research Article The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types. Public Library of Science 2016-06-30 /pmc/articles/PMC4928779/ /pubmed/27362409 http://dx.doi.org/10.1371/journal.pone.0158238 Text en © 2016 Yiangou et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yiangou, Loukia
Montandon, Ruddy
Modrzynska, Katarzyna
Rosen, Barry
Bushell, Wendy
Hale, Christine
Billker, Oliver
Rayner, Julian C.
Pance, Alena
A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
title A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
title_full A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
title_fullStr A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
title_full_unstemmed A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
title_short A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
title_sort stem cell strategy identifies glycophorin c as a major erythrocyte receptor for the rodent malaria parasite plasmodium berghei
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928779/
https://www.ncbi.nlm.nih.gov/pubmed/27362409
http://dx.doi.org/10.1371/journal.pone.0158238
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