biostudies-literatureWang JLthe Research Fund of Shanxi Province for Introduced High-level Leading Talentsthe Special Research Fund of Shanxi Agricultural University for High-level TalentsNational Natural Science Foundation of Chinathe Natural Science Foundation of Gansu Province, Chinathe Research Funding from the Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesNational Key Research and Development Program of Chinae1013475https://www.ebi.ac.uk/biostudies/studies/S-EPMC12425318biostudies-literatureUnknown21(9)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 phosphorylated proteins. Among these, DCS1 and DCS2 were prioritized as potential effectors. While phosphomimetic and non-phosphorylatable mutations in DCS1 and DPLoS pathogensThe PP2A-2 holoenzyme orchestrates daughter cell emergence during cytokinesis in Toxoplasma gondii.PMC124253182021XG0012022YFD1800200 and 2022YFD1800201RFSXIHLT20210123JRRA1479 and 23JRRA555CAAS-ASTIP-JBGS-2021080123JRRA55332422085Wang MFu BQZhu XQZhang NZElsheikha HMGao JWu XJLi TTWang JLfalseThe PP2A-2 holoenzyme orchestrates daughter cell emergence during cytokinesis in Toxoplasma gondii.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 phosphorylated proteins. Among these, DCS1 and DCS2 were prioritized as potential effectors. While phosphomimetic and non-phosphorylatable mutations in DCS1 and D2025-01-01T00:00:00Z2025 Sep2026-05-26T14:07:31.507Z2026-05-24T03:07:08.695ZS-EPMC124253184090199310.1371/journal.ppat.1013475