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An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites
Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-med...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349850/ https://www.ncbi.nlm.nih.gov/pubmed/28221136 http://dx.doi.org/10.7554/eLife.23485 |
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author | Ito, Daisuke Schureck, Marc A Desai, Sanjay A |
author_facet | Ito, Daisuke Schureck, Marc A Desai, Sanjay A |
author_sort | Ito, Daisuke |
collection | PubMed |
description | Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions. We exclude presumed roles for RhopH2 and CLAG3 in erythrocyte invasion but implicate a RhopH3 contribution either through ligand-receptor interactions or subsequent parasite internalization. These proteins then traffic via an export translocon to the host membrane, where they form a nutrient channel. Knockdown of either RhopH2 or RhopH3 disrupts the entire complex, interfering with organellar targeting and subsequent trafficking. Therapies targeting this complex should attack the pathogen at two critical points in its cycle. DOI: http://dx.doi.org/10.7554/eLife.23485.001 |
format | Online Article Text |
id | pubmed-5349850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-53498502017-03-15 An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites Ito, Daisuke Schureck, Marc A Desai, Sanjay A eLife Cell Biology Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions. We exclude presumed roles for RhopH2 and CLAG3 in erythrocyte invasion but implicate a RhopH3 contribution either through ligand-receptor interactions or subsequent parasite internalization. These proteins then traffic via an export translocon to the host membrane, where they form a nutrient channel. Knockdown of either RhopH2 or RhopH3 disrupts the entire complex, interfering with organellar targeting and subsequent trafficking. Therapies targeting this complex should attack the pathogen at two critical points in its cycle. DOI: http://dx.doi.org/10.7554/eLife.23485.001 eLife Sciences Publications, Ltd 2017-02-21 /pmc/articles/PMC5349850/ /pubmed/28221136 http://dx.doi.org/10.7554/eLife.23485 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 | Cell Biology Ito, Daisuke Schureck, Marc A Desai, Sanjay A An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
title | An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
title_full | An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
title_fullStr | An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
title_full_unstemmed | An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
title_short | An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
title_sort | essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349850/ https://www.ncbi.nlm.nih.gov/pubmed/28221136 http://dx.doi.org/10.7554/eLife.23485 |
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