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A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells

The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molec...

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Autores principales: Yang, Chunlin, Broncel, Malgorzata, Dominicus, Caia, Sampson, Emily, Blakely, William J., Treeck, Moritz, Arrizabalaga, Gustavo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459975/
https://www.ncbi.nlm.nih.gov/pubmed/30976120
http://dx.doi.org/10.1038/s41598-019-42441-1
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author Yang, Chunlin
Broncel, Malgorzata
Dominicus, Caia
Sampson, Emily
Blakely, William J.
Treeck, Moritz
Arrizabalaga, Gustavo
author_facet Yang, Chunlin
Broncel, Malgorzata
Dominicus, Caia
Sampson, Emily
Blakely, William J.
Treeck, Moritz
Arrizabalaga, Gustavo
author_sort Yang, Chunlin
collection PubMed
description The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molecular machinery that drives invasion and egress. While much progress has been made elucidating the protein kinases and substrates central to parasite propagation, little is known about the relevant protein phosphatases. In this study, we focused on the five protein phosphatases that are predicted to be membrane-associated either integrally or peripherally. We have determined that of these only PPM5C, a PP2C family member, localizes to the plasma membrane of Toxoplasma. Disruption of PPM5C results in a slow propagation phenotype in tissue culture. Interestingly, parasites lacking PPM5C divide and undergo egress at a normal rate, but have a deficiency in attaching to host cells. Both membrane localization and phosphatase activity are required for PPM5C’s role in attachment. Phosphoproteomic analysis show relatively few phosphorylation sites being affected by PPM5C deletion in extracellular parasites of which several are found on proteins involved in signaling cascades. This implies that PPM5C is part of a wider regulatory network important for attachment to host cells.
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spelling pubmed-64599752019-04-16 A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells Yang, Chunlin Broncel, Malgorzata Dominicus, Caia Sampson, Emily Blakely, William J. Treeck, Moritz Arrizabalaga, Gustavo Sci Rep Article The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molecular machinery that drives invasion and egress. While much progress has been made elucidating the protein kinases and substrates central to parasite propagation, little is known about the relevant protein phosphatases. In this study, we focused on the five protein phosphatases that are predicted to be membrane-associated either integrally or peripherally. We have determined that of these only PPM5C, a PP2C family member, localizes to the plasma membrane of Toxoplasma. Disruption of PPM5C results in a slow propagation phenotype in tissue culture. Interestingly, parasites lacking PPM5C divide and undergo egress at a normal rate, but have a deficiency in attaching to host cells. Both membrane localization and phosphatase activity are required for PPM5C’s role in attachment. Phosphoproteomic analysis show relatively few phosphorylation sites being affected by PPM5C deletion in extracellular parasites of which several are found on proteins involved in signaling cascades. This implies that PPM5C is part of a wider regulatory network important for attachment to host cells. Nature Publishing Group UK 2019-04-11 /pmc/articles/PMC6459975/ /pubmed/30976120 http://dx.doi.org/10.1038/s41598-019-42441-1 Text en © The Author(s) 2019 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
Yang, Chunlin
Broncel, Malgorzata
Dominicus, Caia
Sampson, Emily
Blakely, William J.
Treeck, Moritz
Arrizabalaga, Gustavo
A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
title A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
title_full A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
title_fullStr A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
title_full_unstemmed A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
title_short A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
title_sort plasma membrane localized protein phosphatase in toxoplasma gondii, ppm5c, regulates attachment to host cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459975/
https://www.ncbi.nlm.nih.gov/pubmed/30976120
http://dx.doi.org/10.1038/s41598-019-42441-1
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