Regulation of Starch Stores by a Ca(2+)-Dependent Protein Kinase Is Essential for Viable Cyst Development in Toxoplasma gondii

Cell Host Microbe. 2015 Dec 9;18(6):670-81. doi: 10.1016/j.chom.2015.11.004.

Abstract

Transmissible stages of Toxoplasma gondii store energy in the form of the carbohydrate amylopectin. Here, we show that the Ca(2+)-dependent protein kinase CDPK2 is a critical regulator of amylopectin metabolism. Increased synthesis and loss of degradation of amylopectin in CDPK2 deficient parasites results in the hyperaccumulation of this sugar polymer. A carbohydrate-binding module 20 (CBM20) targets CDPK2 to amylopectin stores, while the EF-hands regulate CDPK2 kinase activity in response to Ca(2+) to modulate amylopectin levels. We identify enzymes involved in amylopectin turnover whose phosphorylation is dependent on CDPK2 activity. Strikingly, accumulation of massive amylopectin granules in CDPK2-deficient bradyzoite stages leads to gross morphological defects and complete ablation of cyst formation in a mouse model. Together these data show that Ca(2+) signaling regulates carbohydrate metabolism in Toxoplasma and that the post-translational control of this pathway is required for normal cyst development.

MeSH terms

  • Amylopectin / metabolism*
  • Animals
  • Calcium / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Survival
  • Gene Deletion
  • Mice
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Spores, Protozoan / growth & development*
  • Spores, Protozoan / metabolism*
  • Toxoplasma / growth & development*
  • Toxoplasma / metabolism*
  • Toxoplasmosis, Animal
  • Virulence

Substances

  • CDPK2 protein, Toxoplasma gondii
  • Calcium-Binding Proteins
  • Protozoan Proteins
  • Amylopectin
  • Protein Kinases
  • Calcium