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Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton

Adherence of Plasmodium falciparum‐infected erythrocytes to host endothelium is conferred through the parasite‐derived virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1), the major contributor to malaria severity. PfEMP1 located at knob structures on the erythrocyte surface is an...

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Autores principales: Oberli, Alexander, Zurbrügg, Laura, Rusch, Sebastian, Brand, Françoise, Butler, Madeleine E., Day, Jemma L., Cutts, Erin E., Lavstsen, Thomas, Vakonakis, Ioannis, Beck, Hans‐Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103180/
https://www.ncbi.nlm.nih.gov/pubmed/26916885
http://dx.doi.org/10.1111/cmi.12583
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author Oberli, Alexander
Zurbrügg, Laura
Rusch, Sebastian
Brand, Françoise
Butler, Madeleine E.
Day, Jemma L.
Cutts, Erin E.
Lavstsen, Thomas
Vakonakis, Ioannis
Beck, Hans‐Peter
author_facet Oberli, Alexander
Zurbrügg, Laura
Rusch, Sebastian
Brand, Françoise
Butler, Madeleine E.
Day, Jemma L.
Cutts, Erin E.
Lavstsen, Thomas
Vakonakis, Ioannis
Beck, Hans‐Peter
author_sort Oberli, Alexander
collection PubMed
description Adherence of Plasmodium falciparum‐infected erythrocytes to host endothelium is conferred through the parasite‐derived virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1), the major contributor to malaria severity. PfEMP1 located at knob structures on the erythrocyte surface is anchored to the cytoskeleton, and the Plasmodium helical interspersed subtelomeric (PHIST) gene family plays a role in many host cell modifications including binding the intracellular domain of PfEMP1. Here, we show that conditional reduction of the PHIST protein PFE1605w strongly reduces adhesion of infected erythrocytes to the endothelial receptor CD36. Adhesion to other endothelial receptors was less affected or even unaltered by PFE1605w depletion, suggesting that PHIST proteins might be optimized for subsets of PfEMP1 variants. PFE1605w does not play a role in PfEMP1 transport, but it directly interacts with both the intracellular segment of PfEMP1 and with cytoskeletal components. This is the first report of a PHIST protein interacting with key molecules of the cytoadherence complex and the host cytoskeleton, and this functional role seems to play an essential role in the pathology of P. falciparum.
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spelling pubmed-51031802016-11-16 Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton Oberli, Alexander Zurbrügg, Laura Rusch, Sebastian Brand, Françoise Butler, Madeleine E. Day, Jemma L. Cutts, Erin E. Lavstsen, Thomas Vakonakis, Ioannis Beck, Hans‐Peter Cell Microbiol Original Articles Adherence of Plasmodium falciparum‐infected erythrocytes to host endothelium is conferred through the parasite‐derived virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1), the major contributor to malaria severity. PfEMP1 located at knob structures on the erythrocyte surface is anchored to the cytoskeleton, and the Plasmodium helical interspersed subtelomeric (PHIST) gene family plays a role in many host cell modifications including binding the intracellular domain of PfEMP1. Here, we show that conditional reduction of the PHIST protein PFE1605w strongly reduces adhesion of infected erythrocytes to the endothelial receptor CD36. Adhesion to other endothelial receptors was less affected or even unaltered by PFE1605w depletion, suggesting that PHIST proteins might be optimized for subsets of PfEMP1 variants. PFE1605w does not play a role in PfEMP1 transport, but it directly interacts with both the intracellular segment of PfEMP1 and with cytoskeletal components. This is the first report of a PHIST protein interacting with key molecules of the cytoadherence complex and the host cytoskeleton, and this functional role seems to play an essential role in the pathology of P. falciparum. John Wiley and Sons Inc. 2016-04-26 2016-10 /pmc/articles/PMC5103180/ /pubmed/26916885 http://dx.doi.org/10.1111/cmi.12583 Text en © 2016 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Oberli, Alexander
Zurbrügg, Laura
Rusch, Sebastian
Brand, Françoise
Butler, Madeleine E.
Day, Jemma L.
Cutts, Erin E.
Lavstsen, Thomas
Vakonakis, Ioannis
Beck, Hans‐Peter
Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
title Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
title_full Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
title_fullStr Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
title_full_unstemmed Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
title_short Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
title_sort plasmodium falciparum plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor p. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103180/
https://www.ncbi.nlm.nih.gov/pubmed/26916885
http://dx.doi.org/10.1111/cmi.12583
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