Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for Plasmodium yoelii liver-stage development
Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for Plasmodium yoelii liver-stage development
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DOI：
10.1111/mmi.12485
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发表时间：
2014-02-01
影响因子：
3.6
通讯作者：
Vaughan, Ashley M.
中科院分区：
文献类型：
--
作者：
Lindner, Scott E.;Sartain, Mark J.;Vaughan, Ashley M.
疟疾寄生虫从其宿主中吸收营养，但也具有从头合成大分子的酶途径。其中一个途径是顶质体靶向的II型脂肪酸合成，这是啮齿动物疟疾肝脏晚期发育所必需的。这是可能的，在顶质体中合成的脂肪酸最终被纳入膜磷脂外裂殖子形成所必需的。我们假设这些合成的脂肪酸被用于顶质体靶向磷脂酸合成，磷脂前体。磷脂酸通常在三步反应中利用三种酶合成：甘油3-磷酸脱氢酶、甘油3-磷酸酰基转移酶和溶血磷脂酸酰基转移酶。疟原虫基因组被预测港口基因为顶质体和胞质/内质网靶向磷脂酸合成。我们的研究表明，顶质体靶向约氏疟原虫甘油3-磷酸脱氢酶和甘油3-磷酸酰基转移酶只在肝脏发育阶段表达，缺失编码基因导致肝脏晚期生长停滞和裂殖子分化缺乏。然而，预测的顶质体靶向溶血磷脂酸酰基转移酶基因是难删除的，在整个寄生虫的生命周期中只在内质网中表达。我们的研究结果表明，约氏疟原虫有一个不完整的尖质体靶向磷脂酸合成途径，这是必不可少的肝脏阶段的成熟。
Malaria parasites scavenge nutrients from their host but also harbour enzymatic pathways for de novo macromolecule synthesis. One such pathway is apicoplast-targeted type II fatty acid synthesis, which is essential for late liver-stage development in rodent malaria. It is likely that fatty acids synthesized in the apicoplast are ultimately incorporated into membrane phospholipids necessary for exoerythrocytic merozoite formation. We hypothesized that these synthesized fatty acids are being utilized for apicoplast-targeted phosphatidic acid synthesis, the phospholipid precursor. Phosphatidic acid is typically synthesized in a three-step reaction utilizing three enzymes: glycerol 3-phosphate dehydrogenase, glycerol 3-phosphate acyltransferase and lysophosphatidic acid acyltransferase. The Plasmodium genome is predicted to harbour genes for both apicoplast- and cytosol/endoplasmic reticulum-targeted phosphatidic acid synthesis. Our research shows that apicoplast-targeted Plasmodium yoelii glycerol 3-phosphate dehydrogenase and glycerol 3-phosphate acyltransferase are expressed only during liver-stage development and deletion of the encoding genes resulted in late liver-stage growth arrest and lack of merozoite differentiation. However, the predicted apicoplast-targeted lysophosphatidic acid acyltransferase gene was refractory to deletion and was expressed solely in the endoplasmic reticulum throughout the parasite life cycle. Our results suggest that P.yoelii has an incomplete apicoplast-targeted phosphatidic acid synthesis pathway that is essential for liver-stage maturation.