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The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii

Phenotypic switching between tachyzoite and bradyzoite is the fundamental mechanism underpinning the pathogenicity and adaptability of the protozoan parasite Toxoplasma gondii. Although accumulation of cytoplasmic starch granules is a hallmark of the quiescent bradyzoite stage, the regulatory factor...

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Autores principales: Wang, Jin-Lei, Li, Ting-Ting, Elsheikha, Hany M., Liang, Qin-Li, Zhang, Zhi-Wei, Wang, Meng, Sibley, L. David, Zhu, Xing-Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9729606/
https://www.ncbi.nlm.nih.gov/pubmed/36476594
http://dx.doi.org/10.1038/s41467-022-35267-5
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author Wang, Jin-Lei
Li, Ting-Ting
Elsheikha, Hany M.
Liang, Qin-Li
Zhang, Zhi-Wei
Wang, Meng
Sibley, L. David
Zhu, Xing-Quan
author_facet Wang, Jin-Lei
Li, Ting-Ting
Elsheikha, Hany M.
Liang, Qin-Li
Zhang, Zhi-Wei
Wang, Meng
Sibley, L. David
Zhu, Xing-Quan
author_sort Wang, Jin-Lei
collection PubMed
description Phenotypic switching between tachyzoite and bradyzoite is the fundamental mechanism underpinning the pathogenicity and adaptability of the protozoan parasite Toxoplasma gondii. Although accumulation of cytoplasmic starch granules is a hallmark of the quiescent bradyzoite stage, the regulatory factors and mechanisms contributing to amylopectin storage in bradyzoites are incompletely known. Here, we show that T. gondii protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit PP2A-C, a scaffold subunit PP2A-A and a regulatory subunit PP2A-B. Disruption of any of these subunits increased starch accumulation and blocked the tachyzoite-to-bradyzoite differentiation. PP2A contributes to the regulation of amylopectin metabolism via dephosphorylation of calcium-dependent protein kinase 2 at S679. Phosphoproteomics identified several putative PP2A holoenzyme substrates that are involved in bradyzoite differentiation. Our findings provide novel insight into the role of PP2A as a key regulator of starch metabolism and bradyzoite differentiation in T. gondii.
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spelling pubmed-97296062022-12-09 The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii Wang, Jin-Lei Li, Ting-Ting Elsheikha, Hany M. Liang, Qin-Li Zhang, Zhi-Wei Wang, Meng Sibley, L. David Zhu, Xing-Quan Nat Commun Article Phenotypic switching between tachyzoite and bradyzoite is the fundamental mechanism underpinning the pathogenicity and adaptability of the protozoan parasite Toxoplasma gondii. Although accumulation of cytoplasmic starch granules is a hallmark of the quiescent bradyzoite stage, the regulatory factors and mechanisms contributing to amylopectin storage in bradyzoites are incompletely known. Here, we show that T. gondii protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit PP2A-C, a scaffold subunit PP2A-A and a regulatory subunit PP2A-B. Disruption of any of these subunits increased starch accumulation and blocked the tachyzoite-to-bradyzoite differentiation. PP2A contributes to the regulation of amylopectin metabolism via dephosphorylation of calcium-dependent protein kinase 2 at S679. Phosphoproteomics identified several putative PP2A holoenzyme substrates that are involved in bradyzoite differentiation. Our findings provide novel insight into the role of PP2A as a key regulator of starch metabolism and bradyzoite differentiation in T. gondii. Nature Publishing Group UK 2022-12-08 /pmc/articles/PMC9729606/ /pubmed/36476594 http://dx.doi.org/10.1038/s41467-022-35267-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Jin-Lei
Li, Ting-Ting
Elsheikha, Hany M.
Liang, Qin-Li
Zhang, Zhi-Wei
Wang, Meng
Sibley, L. David
Zhu, Xing-Quan
The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
title The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
title_full The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
title_fullStr The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
title_full_unstemmed The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
title_short The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
title_sort protein phosphatase 2a holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in toxoplasma gondii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9729606/
https://www.ncbi.nlm.nih.gov/pubmed/36476594
http://dx.doi.org/10.1038/s41467-022-35267-5
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