Plasmodium DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.
Plasmodium DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.
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DOI：
10.26508/lsa.202000879
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发表时间：
2020-12
影响因子：
4.4
通讯作者：
Tewari R
中科院分区：
文献类型：
--
作者：
Guttery DS;Pandey R;Ferguson DJ;Wall RJ;Brady D;Gupta D;Holder AA;Tewari R
疟原虫DEH定位于ER，基因缺失导致发育中的卵囊变性和蚊子中肠中孢子生殖的完全消融，阻断传播。细胞使用脂肪酸（FA）进行膜生物合成，能量储存和信号分子的产生。3-羟酰基-CoA脱氢酶-DEH-是极长链脂肪酸合成的关键组分。在这里，我们进一步深入研究了DEH的位置和功能，应用计算机分析，活细胞成像，反向遗传学和超微结构分析，使用小鼠疟疾模型伯氏疟原虫。DEH在真核生物中是进化保守的，在疟原虫属中具有单个DEH。在其他研究的真核生物中有多达三个直系同源物。DEH-GFP活细胞成像显示在整个生命周期中强烈的GFP荧光，在细胞质中具有局部表达区域，并且在细胞核周围具有与ER标记物共定位的圆环图案。从感染后第10天开始，Δdeh突变体与WT对照相比，卵囊大小显示出较小但显著的减小，并且内有丝分裂细胞分裂和孢子生殖被完全消除，阻断了寄生虫从蚊子传播到脊椎动物宿主。超微结构分析证实Δdeh卵囊退化，子孢子完全不出芽。总体而言，DEH是进化保守的，定位于ER，并在孢子生殖中起着至关重要的作用。
Plasmodium DEH localizes to the ER, with gene deletion resulting in degeneration of developing oocysts and complete ablation of sporogony in the mosquito midgut, blocking transmission. Cells use fatty acids (FAs) for membrane biosynthesis, energy storage, and the generation of signaling molecules. 3-hydroxyacyl-CoA dehydratase—DEH—is a key component of very long chain fatty acid synthesis. Here, we further characterized in-depth the location and function of DEH, applying in silico analysis, live cell imaging, reverse genetics, and ultrastructure analysis using the mouse malaria model Plasmodium berghei. DEH is evolutionarily conserved across eukaryotes, with a single DEH in Plasmodium spp. and up to three orthologs in the other eukaryotes studied. DEH-GFP live-cell imaging showed strong GFP fluorescence throughout the life-cycle, with areas of localized expression in the cytoplasm and a circular ring pattern around the nucleus that colocalized with ER markers. Δdeh mutants showed a small but significant reduction in oocyst size compared with WT controls from day 10 postinfection onwards, and endomitotic cell division and sporogony were completely ablated, blocking parasite transmission from mosquito to vertebrate host. Ultrastructure analysis confirmed degeneration of Δdeh oocysts, and a complete lack of sporozoite budding. Overall, DEH is evolutionarily conserved, localizes to the ER, and plays a crucial role in sporogony.
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影响因子：
3.5
作者：
Li, DX;Gonzalez, O;Roberts, R
通讯作者：
Roberts, R
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Kunst, Ljerka
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Kappe SH
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30.3
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Yu M;Kumar TR;Nkrumah LJ;Coppi A;Retzlaff S;Li CD;Kelly BJ;Moura PA;Lakshmanan V;Freundlich JS;Valderramos JC;Vilcheze C;Siedner M;Tsai JH;Falkard B;Sidhu AB;Purcell LA;Gratraud P;Kremer L;Waters AP;Schiehser G;Jacobus DP;Janse CJ;Ager A;Jacobs WR Jr;Sacchettini JC;Heussler V;Sinnis P;Fidock DA
通讯作者：
Fidock DA