PP6C

TgPP6C is the catalytic subunit of the Toxoplasma gondii protein phosphatase 6 complex that coordinates synchronous daughter-cell formation during endodyogeny (PMID:38091362). It assembles with the regulatory subunit TgPP6R into a holoenzyme, whereas the predicted structural subunit TgPP6S does not co-assemble with TgPP6C and TgPP6R (PMID:38091362). Its phosphatase activity depends on six conserved catalytic motifs required for efficient endodyogeny, and phosphoproteomics after TgPP6C ablation shows it predominantly controls the phosphorylation status of cell cycle regulatory proteins (PMID:38091362). In the type I RH strain, TgPP6C is essential for parasite growth and replication—its loss impairs synchronous division and produces disordered rosettes—and is required for full virulence in mice (PMID:38091362). Direct dephosphorylation of individual substrates has not been demonstrated in the available corpus.

1. 2023 Medium

   Defining the composition of the T. gondii PP6 complex established that TgPP6C partners with the regulatory subunit TgPP6R but not with the predicted structural subunit TgPP6S, refining the holoenzyme architecture.

   Evidence Co-immunoprecipitation / complex assembly assay in RH strain

   PMID:38091362

   Open questions at the time

   • TgPP6C–TgPP6R interaction reported as 'likely' from a single Co-IP without reciprocal validation
   • stoichiometry and structural basis of assembly not resolved
   • reason TgPP6S fails to co-assemble not determined
2. 2023 High

   Conditional ablation showed TgPP6C is essential for parasite growth and that its loss disrupts synchronous daughter-cell division, placing the phosphatase at the heart of endodyogeny coordination.

   Evidence Conditional knockdown/knockout with growth, morphology, and cell cycle readouts in RH strain

   PMID:38091362

   Open questions at the time

   • mechanistic link between phosphatase loss and rosette disorder not defined
   • cell cycle stage of the block not pinpointed
3. 2023 High

   Mutagenesis of the six conserved catalytic motifs demonstrated that catalytic phosphatase activity, not merely the protein's scaffolding, is required for efficient endodyogeny.

   Evidence Site-directed mutagenesis of catalytic motifs plus endodyogeny phenotype in RH strain

   PMID:38091362

   Open questions at the time

   • individual contributions of each motif not dissected
   • residual activity of mutants not quantified
4. 2023 Medium

   Phosphoproteomics after ablation identified cell cycle regulators as the predominant class of proteins whose phosphorylation TgPP6C controls, providing the substrate landscape for its division role.

   Evidence Quantitative phosphoproteomics following conditional ablation in RH strain

   PMID:38091362

   Open questions at the time

   • substrates inferred from altered phosphorylation, not direct dephosphorylation assays
   • no individual substrate validated in vitro
   • direct vs indirect effects not distinguished
5. 2023 Medium

   Deletion in the type I RH strain attenuated virulence in mice, connecting the replication defect to a requirement for full in vivo pathogenicity.

   Evidence Mouse infection model with TgPP6C-deficient RH strain

   PMID:38091362

   Open questions at the time

   • not tested in other strains or acute/chronic stages
   • whether attenuation is solely from replication defect not established

• Direct enzyme-substrate relationships and the biochemical mechanism by which TgPP6C dephosphorylation coordinates daughter-cell formation remain to be defined.
• no direct dephosphorylation assay for any candidate substrate
• role of TgPP6R in substrate targeting unknown
• structural model of holoenzyme absent