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The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence

ABSTRACT: Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Toxoplasma Gondii Veg

TISSUE(S): Whole Body

SUBMITTER: Qinli Liang

LAB HEAD: xingquan zhu

PROVIDER: PXD041907 | Pride | 2023-11-28

REPOSITORIES: Pride

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Project description:Distinct genotypic and pathogenicity differences exist between strains of the opportunistic protozoan Toxoplasma gondii. The label-free quantitative acetylomics approach was applied to investigate the differences in the level of acetylation between RH strain, PRU strain and PYS strain of T. gondii. The results showed that lysine acetylation in RH strain was the largest (458 acetylated proteins) among the three strains. The PYS strain had the second-largest acetylome (188 acetylated proteins), whereas lysine acetylation in PRU strain (115 acetylated proteins) was the smallest. Motif analysis revealed four, three and four motifs enriched from lysine acetylation sequences in RH strain, PRU strain and PYS strain respectively, suggesting specificity of acetyltransferases in these strains. Our analysis also identified 15 DAPs (differentially expressed acetylated proteins), 3 DAPs and 26 DAPs in RH strain vs PRU strain, PRU strain vs PYS strain and PYS strain vs RH strain, respectively. Compared with PYS strain and PRU strain, histone acetyltransferase and glycyl-tRNA synthase had higher expression levels in RH strain, reflecting genotype-specific differences in stress tolerance. These findings provide novel insight into the acetylomic profiles of major genotypes of T. gondii and provide an important resource for further analysis of the roles of the acetylated parasite proteins in the regulation of cellular functions.

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