کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4360902 | 1301327 | 2015 | 12 صفحه PDF | دانلود رایگان |
• The Toxoplasma kinase CDPK2 has functional Ca2+- and carbohydrate-binding domains
• CDPK2 deficiency causes unchecked accumulation of starch in Toxoplasma parasites
• Phosphorylation of several starch-metabolic enzymes relies on CDPK2 activity
• Loss of CDPK2 results in starch hyperaccumulation and death of chronic-stage parasites
SummaryTransmissible 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.
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Journal: - Volume 18, Issue 6, 9 December 2015, Pages 670–681