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The PP2A-2 holoenzyme orchestrates daughter cell emergence during cytokinesis in Toxoplasma gondii

文献类型： 外文期刊

作者： Jin Lei Wang;Meng Wang;Nian Zhang Zhang;Ting Ting Li;Jin Gao;Xiao Jing Wu;Bao Quan Fu;Hany M. Elsheikha;Xing Quan Zhu

作者机构：

期刊名称： PLOS Pathogens

ISSN： 1553-7374

年卷期： 2025 年 21 卷 9 September 期

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收录情况： SCIE（2025版）

摘要： Toxoplasma gondii is a significant pathogen in both humans and animals, with disease progression driven by the rapid proliferation of its tachyzoite stage. In this study, we identify the PP2A-2 holoenzyme as a key regulator of daughter cell emergence during parasite division. This holoenzyme, likely composed of the regulatory subunit TgPR48 (PP2A-B2), the catalytic subunit PP2A-C2, and the scaffolding subunit PP2A-A2, is essential for proper cytokinesis. Disruption of any single component severely impairs daughter cell separation and emergence. Phosphoproteomic analysis following PP2A-C2 depletion revealed numerous differentially phosphoryated proteins. Among these, DCS1 and DCS2 were prioritized as potential effectors. While phosphomimetic and non-phosphorylatable mutations in DCS1 and DCS2 did not significantly impair their function, depletion of either protein disrupted TgPR48 ocalization. Interestingly, TgPR48 overexpression partially rescued the phenotypes associated with DCS2 loss, but not DCS1, indicating divergence in their downstream pathways and implicating additional, yet unidentified, substrates. These findings establish PP2A-2–mediated dephosphorylation as a central mechanism in regulating achyzoite cytokinesis and highlight a promising regulatory axis for therapeutic intervention against T. gondii.

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