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EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites

Intracellular malaria parasites grow in a vacuole delimited by the parasitophorous vacuolar membrane (PVM). This membrane fulfils critical roles for survival of the parasite in its intracellular niche such as in protein export and nutrient acquisition. Using a conditional knockout (KO), we here demo...

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Autores principales: Mesén-Ramírez, Paolo, Bergmann, Bärbel, Tran, Thuy Tuyen, Garten, Matthias, Stäcker, Jan, Naranjo-Prado, Isabel, Höhn, Katharina, Zimmerberg, Joshua, Spielmann, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786648/
https://www.ncbi.nlm.nih.gov/pubmed/31568532
http://dx.doi.org/10.1371/journal.pbio.3000473
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author Mesén-Ramírez, Paolo
Bergmann, Bärbel
Tran, Thuy Tuyen
Garten, Matthias
Stäcker, Jan
Naranjo-Prado, Isabel
Höhn, Katharina
Zimmerberg, Joshua
Spielmann, Tobias
author_facet Mesén-Ramírez, Paolo
Bergmann, Bärbel
Tran, Thuy Tuyen
Garten, Matthias
Stäcker, Jan
Naranjo-Prado, Isabel
Höhn, Katharina
Zimmerberg, Joshua
Spielmann, Tobias
author_sort Mesén-Ramírez, Paolo
collection PubMed
description Intracellular malaria parasites grow in a vacuole delimited by the parasitophorous vacuolar membrane (PVM). This membrane fulfils critical roles for survival of the parasite in its intracellular niche such as in protein export and nutrient acquisition. Using a conditional knockout (KO), we here demonstrate that the abundant integral PVM protein exported protein 1 (EXP1) is essential for parasite survival but that this is independent of its previously postulated function as a glutathione S-transferase (GST). Patch-clamp experiments indicated that EXP1 is critical for the nutrient-permeable channel activity at the PVM. Loss of EXP1 abolished the correct localisation of EXP2, a pore-forming protein required for the nutrient-permeable channel activity and protein export at the PVM. Unexpectedly, loss of EXP1 affected only the nutrient-permeable channel activity of the PVM but not protein export. Parasites with low levels of EXP1 became hypersensitive to low nutrient conditions, indicating that EXP1 indeed is needed for nutrient uptake and experimentally confirming the long-standing hypothesis that the channel activity measured at the PVM is required for parasite nutrient acquisition. Hence, EXP1 is specifically required for the functional expression of EXP2 as the nutrient-permeable channel and is critical for the metabolite supply of malaria parasites.
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spelling pubmed-67866482019-10-19 EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites Mesén-Ramírez, Paolo Bergmann, Bärbel Tran, Thuy Tuyen Garten, Matthias Stäcker, Jan Naranjo-Prado, Isabel Höhn, Katharina Zimmerberg, Joshua Spielmann, Tobias PLoS Biol Research Article Intracellular malaria parasites grow in a vacuole delimited by the parasitophorous vacuolar membrane (PVM). This membrane fulfils critical roles for survival of the parasite in its intracellular niche such as in protein export and nutrient acquisition. Using a conditional knockout (KO), we here demonstrate that the abundant integral PVM protein exported protein 1 (EXP1) is essential for parasite survival but that this is independent of its previously postulated function as a glutathione S-transferase (GST). Patch-clamp experiments indicated that EXP1 is critical for the nutrient-permeable channel activity at the PVM. Loss of EXP1 abolished the correct localisation of EXP2, a pore-forming protein required for the nutrient-permeable channel activity and protein export at the PVM. Unexpectedly, loss of EXP1 affected only the nutrient-permeable channel activity of the PVM but not protein export. Parasites with low levels of EXP1 became hypersensitive to low nutrient conditions, indicating that EXP1 indeed is needed for nutrient uptake and experimentally confirming the long-standing hypothesis that the channel activity measured at the PVM is required for parasite nutrient acquisition. Hence, EXP1 is specifically required for the functional expression of EXP2 as the nutrient-permeable channel and is critical for the metabolite supply of malaria parasites. Public Library of Science 2019-09-30 /pmc/articles/PMC6786648/ /pubmed/31568532 http://dx.doi.org/10.1371/journal.pbio.3000473 Text en https://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 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Mesén-Ramírez, Paolo
Bergmann, Bärbel
Tran, Thuy Tuyen
Garten, Matthias
Stäcker, Jan
Naranjo-Prado, Isabel
Höhn, Katharina
Zimmerberg, Joshua
Spielmann, Tobias
EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
title EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
title_full EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
title_fullStr EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
title_full_unstemmed EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
title_short EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
title_sort exp1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786648/
https://www.ncbi.nlm.nih.gov/pubmed/31568532
http://dx.doi.org/10.1371/journal.pbio.3000473
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