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The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake

Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeabilit...

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Autores principales: Sherling, Emma S, Knuepfer, Ellen, Brzostowski, Joseph A, Miller, Louis H, Blackman, Michael J, van Ooij, Christiaan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365315/
https://www.ncbi.nlm.nih.gov/pubmed/28252384
http://dx.doi.org/10.7554/eLife.23239
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author Sherling, Emma S
Knuepfer, Ellen
Brzostowski, Joseph A
Miller, Louis H
Blackman, Michael J
van Ooij, Christiaan
author_facet Sherling, Emma S
Knuepfer, Ellen
Brzostowski, Joseph A
Miller, Louis H
Blackman, Michael J
van Ooij, Christiaan
author_sort Sherling, Emma S
collection PubMed
description Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeability pathways (NPP) including a Plasmodium surface anion channel (PSAC). RhopH1/Clag3, one member of the three-protein RhopH complex, is important for PSAC/NPP activity. However, the roles of the other members of the RhopH complex in PSAC/NPP establishment are unknown and it is unclear whether any of the RhopH proteins play a role in invasion. Here we demonstrate that RhopH3, the smallest component of the complex, is essential for parasite survival. Conditional truncation of RhopH3 substantially reduces invasive capacity. Those mutant parasites that do invade are defective in nutrient import and die. Our results identify a dual role for RhopH3 that links erythrocyte invasion to formation of the PSAC/NPP essential for parasite survival within host erythrocytes. DOI: http://dx.doi.org/10.7554/eLife.23239.001
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spelling pubmed-53653152017-03-27 The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake Sherling, Emma S Knuepfer, Ellen Brzostowski, Joseph A Miller, Louis H Blackman, Michael J van Ooij, Christiaan eLife Microbiology and Infectious Disease Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeability pathways (NPP) including a Plasmodium surface anion channel (PSAC). RhopH1/Clag3, one member of the three-protein RhopH complex, is important for PSAC/NPP activity. However, the roles of the other members of the RhopH complex in PSAC/NPP establishment are unknown and it is unclear whether any of the RhopH proteins play a role in invasion. Here we demonstrate that RhopH3, the smallest component of the complex, is essential for parasite survival. Conditional truncation of RhopH3 substantially reduces invasive capacity. Those mutant parasites that do invade are defective in nutrient import and die. Our results identify a dual role for RhopH3 that links erythrocyte invasion to formation of the PSAC/NPP essential for parasite survival within host erythrocytes. DOI: http://dx.doi.org/10.7554/eLife.23239.001 eLife Sciences Publications, Ltd 2017-03-02 /pmc/articles/PMC5365315/ /pubmed/28252384 http://dx.doi.org/10.7554/eLife.23239 Text en http://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Microbiology and Infectious Disease
Sherling, Emma S
Knuepfer, Ellen
Brzostowski, Joseph A
Miller, Louis H
Blackman, Michael J
van Ooij, Christiaan
The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
title The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
title_full The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
title_fullStr The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
title_full_unstemmed The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
title_short The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake
title_sort plasmodium falciparum rhoptry protein rhoph3 plays essential roles in host cell invasion and nutrient uptake
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365315/
https://www.ncbi.nlm.nih.gov/pubmed/28252384
http://dx.doi.org/10.7554/eLife.23239
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