Research Publications


Regulation of starch stores by a Ca2+-dependent protein kinase is essential for viable cyst development in Toxoplasma gondii

Uboldi, Alessandro D; McCoy, James M; Blume, Martin; Gerlic, Motti; Ferguson, David J P; 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
Cell Host & Microbe
Journal Article
Transmissible stages of Toxoplasma gondii store energy in the form of the carbohydrate amylopectin. Here, we show that the Ca2+-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 Ca2+ 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 Ca2+ signaling regulates carbohydrate metabolism in Toxoplasma and that the post-translational control of this pathway is required for normal cyst development.
Infection and Immunity; Systems Biology and Personalised Medicine; Inflammation
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