PP6R

TgPP6R is the regulatory subunit of a PP6-type protein phosphatase holoenzyme in Toxoplasma gondii, where it co-assembles with the catalytic subunit TgPP6C, while the predicted structural subunit TgPP6S does not join this complex (PMID:38091362). TgPP6R is essential for parasite growth and replication, its ablation impairing both processes (PMID:38091362). Beyond its assignment as the PP6 regulatory subunit and its essentiality, the specific substrate recognition or regulatory function contributed by TgPP6R itself has not been characterized in the available corpus.

1. 2023 Medium

   Establishing the composition of the Toxoplasma PP6 phosphatase was needed to define which subunits form a functional holoenzyme; co-assembly studies showed TgPP6R and the catalytic TgPP6C associate while the predicted structural TgPP6S does not.

   Evidence Co-assembly/complex formation assay in T. gondii RH, with a negative result for TgPP6S as orthogonal support

   PMID:38091362

   Open questions at the time

   • Precise co-IP method and stoichiometry not detailed
   • Direct interaction interface between TgPP6R and TgPP6C not mapped
   • Role of TgPP6S in the pathway left undefined
2. 2023 Medium

   Whether the regulatory subunit is dispensable was unknown; conditional ablation demonstrated TgPP6R is essential for parasite growth and replication.

   Evidence Conditional knockdown/ablation with growth and replication readout in T. gondii RH

   PMID:38091362

   Open questions at the time

   • The specific step of replication blocked by TgPP6R loss not resolved
   • Whether essentiality reflects holoenzyme assembly versus an independent function is unclear
3. 2023 High

   To connect the phosphatase to a cellular process, ablation and motif mutagenesis of the catalytic subunit TgPP6C showed it is required for synchronous daughter-cell division during endodyogeny and for ordered rosette formation.

   Evidence Conditional ablation, microscopy of endodyogeny, and mutagenesis of six conserved catalytic motifs in T. gondii RH

   PMID:38091362

   Open questions at the time

   • Findings concern TgPP6C, not TgPP6R directly
   • How endodyogeny synchrony is mechanistically enforced by the phosphatase is unresolved
4. 2023 Medium

   To identify the molecular targets of the phosphatase, phosphoproteomics after TgPP6C ablation showed it predominantly controls phosphorylation of cell cycle regulatory proteins, defining PP6 as a dephosphorylase of cell cycle regulators.

   Evidence Mass spectrometry-based phosphoproteomics following conditional knockdown of TgPP6C in T. gondii RH

   PMID:38091362

   Open questions at the time

   • No direct substrate validated by reconstitution
   • Substrates were mapped via the catalytic subunit, not through TgPP6R