Affinage · Toxoplasma gondii

PP2A-A

serine/threonine-protein phosphatase PP2A subunit A · UniProt S8EX93

Annotated
2026-09-11
4 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PP2A-A is the scaffold/structural subunit of Toxoplasma gondii PP2A phosphatase holoenzymes, assembling with a catalytic subunit (PP2A-C) and a variable regulatory subunit (PP2A-B) to form distinct complexes that govern parasite carbohydrate metabolism and division (PMID:36476594). Through a PP2A-A/PP2A-C/PP2A-B holoenzyme, the phosphatase controls amylopectin/starch metabolism by dephosphorylating CDPK2 at S679, and disruption of any single subunit — including PP2A-A — causes starch over-accumulation and blocks tachyzoite-to-bradyzoite differentiation (PMID:36476594). Assembly and activity of the PP2A A/C core are promoted by PTPA, which forms a ternary complex with the A and C subunits and is needed for proliferation, invasion, gliding, and cyst formation (PMID:40498010). Nothing further is known about PP2A-A-specific mechanistic roles in Toxoplasma gondii from the remaining literature.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2022 High

    Defining the parasite's own PP2A-A/B/C holoenzyme and a phospho-substrate answered what intrinsic process PP2A controls, linking it to starch metabolism and stage differentiation.

    Evidence Genetic disruption of individual subunits, phosphoproteomics identifying CDPK2-S679, and starch accumulation assays

    PMID:36476594

    Open questions at the time
    • Direct dephosphorylation of CDPK2-S679 by the holoenzyme not reconstituted in vitro
    • Additional substrates beyond CDPK2 not enumerated
  2. 2025 Medium

    Identifying PTPA as a ternary partner of the A and C subunits established an upstream regulator that activates PP2A to sustain proliferation, invasion, motility, and differentiation.

    Evidence Reciprocal pull-down assays, conditional PTPA depletion, LB-100 chemical phenocopy, and phenotypic assays

    PMID:40498010

    Open questions at the time
    • Mechanism by which PTPA activates the A/C complex not resolved
    • Whether PTPA acts on all PP2A holoenzymes or a subset unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CDPK2 (SUBSTRATE, S679)PP2A-B (REGULATORY SUBUNIT)PP2A-C (CATALYTIC SUBUNIT)PTPA
Complex memberships
PP2A holoenzyme (PP2A-A scaffold / PP2A-C catalytic / PP2A-B regulatory)PTPA-PP2A A/C ternary complex

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 The T. gondii PP2A holoenzyme is composed of a catalytic subunit PP2A-C, a scaffold subunit PP2A-A, and a regulatory subunit PP2A-B; disruption of any single subunit (including PP2A-A) increases starch accumulation and blocks tachyzoite-to-bradyzoite differentiation. PP2A contributes to amylopectin metabolism via dephosphorylation of calcium-dependent protein kinase 2 (CDPK2) at S679. Genetic disruption of individual subunits, phosphoproteomics, biochemical characterization of holoenzyme composition, in vivo starch accumulation assays Nature communications High 36476594
2025 PTPA (phosphotyrosyl phosphatase activator) forms a ternary complex with PP2A A and C subunits in T. gondii, validated by reciprocal pull-down assays; depletion of PTPA impairs tachyzoite proliferation, invasion, gliding motility, and stress-induced bradyzoite cyst formation, and causes amylopectin accumulation and lipid droplet proliferation. The PP2A inhibitor LB-100 phenocopies PTPA depletion. Reciprocal pull-down assays (ternary complex validation), conditional depletion of PTPA, LB-100 chemical inhibition, phenotypic assays (proliferation, invasion, gliding, cyst formation) Cells Medium 40498010

Source papers

Stage 0 corpus · 4 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii. Nature communications 46 36476594
2025 Live-attenuated Toxoplasma gondii PruΔpp2a-c mutant elicits protective immunity against toxoplasmosis in mice and cats. International journal for parasitology 4 40783178
2023 Converting and hoarding driven by protein phosphorylation in Toxoplasma gondii. Trends in parasitology 1 36804381
2025 PTPA Governs Stress-Responsive Differentiation and Metabolic Homeostasis in Toxoplasma gondii. Cells 0 40498010