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

Cell Host Microbe. 2015 Dec 9;18(6):670-681. doi: 10.1016/j.chom.2015.11.004.

 

Uboldi AD¹, McCoy JM¹, Blume M², Gerlic M¹, Ferguson DJ³, Dagley LF¹, Beahan CT⁴, Stapleton DI⁵, Gooley PR², Bacic A⁴, Masters SL¹, Webb AI¹, McConville MJ², Tonkin CJ⁶.

 

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.
Copyright © 2015 Elsevier Inc. All rights reserved.

PMID:

26651943

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