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Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis

Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apic...

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Autores principales: Tawk, Lina, Dubremetz, Jean-François, Montcourrier, Philippe, Chicanne, Gaëtan, Merezegue, Fabrice, Richard, Véronique, Payrastre, Bernard, Meissner, Markus, Vial, Henri J., Roy, Christian, Wengelnik, Kai, Lebrun, Maryse
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040667/
https://www.ncbi.nlm.nih.gov/pubmed/21379336
http://dx.doi.org/10.1371/journal.ppat.1001286
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author Tawk, Lina
Dubremetz, Jean-François
Montcourrier, Philippe
Chicanne, Gaëtan
Merezegue, Fabrice
Richard, Véronique
Payrastre, Bernard
Meissner, Markus
Vial, Henri J.
Roy, Christian
Wengelnik, Kai
Lebrun, Maryse
author_facet Tawk, Lina
Dubremetz, Jean-François
Montcourrier, Philippe
Chicanne, Gaëtan
Merezegue, Fabrice
Richard, Véronique
Payrastre, Bernard
Meissner, Markus
Vial, Henri J.
Roy, Christian
Wengelnik, Kai
Lebrun, Maryse
author_sort Tawk, Lina
collection PubMed
description Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs.
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spelling pubmed-30406672011-03-04 Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis Tawk, Lina Dubremetz, Jean-François Montcourrier, Philippe Chicanne, Gaëtan Merezegue, Fabrice Richard, Véronique Payrastre, Bernard Meissner, Markus Vial, Henri J. Roy, Christian Wengelnik, Kai Lebrun, Maryse PLoS Pathog Research Article Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs. Public Library of Science 2011-02-17 /pmc/articles/PMC3040667/ /pubmed/21379336 http://dx.doi.org/10.1371/journal.ppat.1001286 Text en Tawk et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tawk, Lina
Dubremetz, Jean-François
Montcourrier, Philippe
Chicanne, Gaëtan
Merezegue, Fabrice
Richard, Véronique
Payrastre, Bernard
Meissner, Markus
Vial, Henri J.
Roy, Christian
Wengelnik, Kai
Lebrun, Maryse
Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis
title Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis
title_full Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis
title_fullStr Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis
title_full_unstemmed Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis
title_short Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis
title_sort phosphatidylinositol 3-monophosphate is involved in toxoplasma apicoplast biogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040667/
https://www.ncbi.nlm.nih.gov/pubmed/21379336
http://dx.doi.org/10.1371/journal.ppat.1001286
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