Regulation of Starch Stores by a Ca2+-Dependent Protein Kinase Is Essential for Viable Cyst Development in Toxoplasma gondii Academic Article uri icon

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.

authors

  • Uboldi, Alessandro D
  • McCoy, James M
  • Blume, Martin
  • Gerlic, Motti
  • Ferguson, David JP
  • Dagley, Laura F
  • Beahan, Cherie T
  • Stapleton, David I
  • Gooley, Paul R
  • Bacic, Antony
  • Masters, Seth L
  • Webb, Andrew I
  • McConville, Malcolm J
  • Tonkin, Christopher J

publication date

  • 2015