PGM2

Toxoplasma gondii PGM2 is a phosphoglucomutase paralog that functions specifically in the high-Ca2+-flux branch of microneme exocytosis (PMID:29202046). Genetic deletion of PGM2 abrogates microneme secretion triggered by the calcium ionophore A23187 while leaving basal constitutive release and phosphatidic acid-triggered secretion intact, placing it selectively downstream of high-Ca2+ signaling (PMID:29202046). This PGM2-dependent secretion is nevertheless dispensable for tachyzoite lytic cycle completion—invasion and egress—and for acute virulence in mice, both alone and in combination with PRP1 deletion (PMID:29202046). The crystal structure of PGM2 has been solved, defining its oligomeric state and active-site features for ligand recognition, and antisense knockdown of PGM expression reduces parasite replication without host cell toxicity (PMID:30345257). Beyond these findings, the enzymatic substrates and the molecular link between PGM2 catalysis and the calcium-triggered secretion machinery have not been characterized in the available corpus.

1. 2017 Medium

   To determine which branch of microneme exocytosis PGM2 acts in, deletion resolved that it is required specifically for high-Ca2+-triggered but not constitutive or phosphatidic acid-triggered secretion.

   Evidence Gene deletion with microneme secretion assays comparing A23187 ionophore and phosphatidic acid stimulation

   PMID:29202046

   Open questions at the time

   • The catalytic substrate and how phosphoglucomutase activity connects to calcium-triggered exocytosis are undefined
   • Single-lab result
2. 2017 Medium

   To test whether PGM2-dependent secretion is essential for the parasite life cycle, single and double (with PRP1) knockouts showed lytic cycle and acute virulence are unaffected, establishing this secretion branch as dispensable for those processes.

   Evidence Single and double gene deletion, plaque/lytic cycle assays, mouse acute infection model

   PMID:29202046

   Open questions at the time

   • Whether PGM2 is required in chronic infection or other life-cycle stages was not tested
   • Functional redundancy with other paralogs not excluded
3. 2018 Medium

   To provide molecular and functional detail beyond genetics, the crystal structure was solved and antisense knockdown confirmed a role in parasite replication.

   Evidence X-ray crystallography and vivoPMO antisense knockdown with parasite replication assay

   PMID:30345257

   Open questions at the time

   • No enzyme kinetics or in vitro demonstration of phosphoglucomutase catalysis reported
   • The structural features are not connected to the secretion phenotype

• How PGM2's phosphoglucomutase activity mechanistically couples to high-Ca2+-triggered microneme exocytosis remains unresolved.
• No substrate or metabolic product linked to the secretion defect
• No identified interaction partners in the secretion machinery
• Subcellular localization relative to micronemes not established in this corpus