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PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes

The disease-causing blood-stage of the Plasmodium falciparum lifecycle begins with invasion of human erythrocytes by merozoites. Many vaccine candidates with key roles in binding to the erythrocyte surface and entry are secreted from the large bulb-like rhoptry organelles at the apical tip of the me...

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Autores principales: Liffner, Benjamin, Frölich, Sonja, Heinemann, Gary K., Liu, Boyin, Ralph, Stuart A., Dixon, Matthew W. A., Gilberger, Tim-Wolf, Wilson, Danny W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075938/
https://www.ncbi.nlm.nih.gov/pubmed/32179747
http://dx.doi.org/10.1038/s41467-020-15127-w
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author Liffner, Benjamin
Frölich, Sonja
Heinemann, Gary K.
Liu, Boyin
Ralph, Stuart A.
Dixon, Matthew W. A.
Gilberger, Tim-Wolf
Wilson, Danny W.
author_facet Liffner, Benjamin
Frölich, Sonja
Heinemann, Gary K.
Liu, Boyin
Ralph, Stuart A.
Dixon, Matthew W. A.
Gilberger, Tim-Wolf
Wilson, Danny W.
author_sort Liffner, Benjamin
collection PubMed
description The disease-causing blood-stage of the Plasmodium falciparum lifecycle begins with invasion of human erythrocytes by merozoites. Many vaccine candidates with key roles in binding to the erythrocyte surface and entry are secreted from the large bulb-like rhoptry organelles at the apical tip of the merozoite. Here we identify an essential role for the conserved protein P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 1 (PfCERLI1) in rhoptry function. We show that PfCERLI1 localises to the cytosolic face of the rhoptry bulb membrane and knockdown of PfCERLI1 inhibits merozoite invasion. While schizogony and merozoite organelle biogenesis appear normal, biochemical techniques and semi-quantitative super-resolution microscopy show that PfCERLI1 knockdown prevents secretion of key rhoptry antigens that coordinate merozoite invasion. PfCERLI1 is a rhoptry associated protein identified to have a direct role in function of this essential merozoite invasion organelle, which has broader implications for understanding apicomplexan invasion biology.
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spelling pubmed-70759382020-03-18 PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes Liffner, Benjamin Frölich, Sonja Heinemann, Gary K. Liu, Boyin Ralph, Stuart A. Dixon, Matthew W. A. Gilberger, Tim-Wolf Wilson, Danny W. Nat Commun Article The disease-causing blood-stage of the Plasmodium falciparum lifecycle begins with invasion of human erythrocytes by merozoites. Many vaccine candidates with key roles in binding to the erythrocyte surface and entry are secreted from the large bulb-like rhoptry organelles at the apical tip of the merozoite. Here we identify an essential role for the conserved protein P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 1 (PfCERLI1) in rhoptry function. We show that PfCERLI1 localises to the cytosolic face of the rhoptry bulb membrane and knockdown of PfCERLI1 inhibits merozoite invasion. While schizogony and merozoite organelle biogenesis appear normal, biochemical techniques and semi-quantitative super-resolution microscopy show that PfCERLI1 knockdown prevents secretion of key rhoptry antigens that coordinate merozoite invasion. PfCERLI1 is a rhoptry associated protein identified to have a direct role in function of this essential merozoite invasion organelle, which has broader implications for understanding apicomplexan invasion biology. Nature Publishing Group UK 2020-03-16 /pmc/articles/PMC7075938/ /pubmed/32179747 http://dx.doi.org/10.1038/s41467-020-15127-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liffner, Benjamin
Frölich, Sonja
Heinemann, Gary K.
Liu, Boyin
Ralph, Stuart A.
Dixon, Matthew W. A.
Gilberger, Tim-Wolf
Wilson, Danny W.
PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
title PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
title_full PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
title_fullStr PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
title_full_unstemmed PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
title_short PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
title_sort pfcerli1 is a conserved rhoptry associated protein essential for plasmodium falciparum merozoite invasion of erythrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075938/
https://www.ncbi.nlm.nih.gov/pubmed/32179747
http://dx.doi.org/10.1038/s41467-020-15127-w
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