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

Abstract

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 sub- strates 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.

Citation

Wang, J.-L., Li, T.-T., Elsheikha, H. M., Liang, Q.-L., Zhang, Z.-W., Wang, M., Sibley, L. D., & Zhu, X.-Q. (2022). The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii. Nature Communications, 13(1), Article 7560. https://doi.org/10.1038/s41467-022-35267-5

• Journal Article Type: Article
• Acceptance Date: Nov 22, 2022
• Online Publication Date: Dec 8, 2022
• Publication Date: Dec 8, 2022
• Deposit Date: Dec 8, 2022
• Publicly Available Date: Dec 8, 2022
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 7560
• DOI: https://doi.org/10.1038/s41467-022-35267-5
• Keywords: General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/14596517
• Publisher URL: https://www.nature.com/articles/s41467-022-35267-5
• Additional Information: Received: 30 March 2022; Accepted: 22 November 2022; First Online: 8 December 2022; : The authors declare no competing interests.