Target of rapamycin-mediated amino acid signaling in mosquito anautogeny
Target of rapamycin-mediated amino acid signaling in mosquito anautogeny
复制标题
DOI：
10.1073/pnas.0403460101
复制
发表时间：
2004-07-20
影响因子：
11.1
通讯作者：
Raikhel, AS
中科院分区：
文献类型：
--
作者：
Hansen, IA;Attardo, GM;Raikhel, AS
蚊子在世界范围内给人类健康造成了巨大的负担。传播疾病的物种使用一种称为异体繁殖的生殖策略，这种策略需要血餐来启动卵子成熟。虽然这一策略对于推动疾病传播很重要，但这种现象背后的分子机制仍然知之甚少。卵黄蛋白前体(YPPs)的产生是卵子成熟的中心事件，被称为卵黄发生。YPP是在脂肪体中合成的，脂肪体是昆虫对脊椎动物肝脏的类似物。蚊子的卵黄发生受类固醇激素20羟基蜕皮酮(20E)的调节。然而，仅有20E本身并不能激活体内的卵黄生成。在这里，我们报告了通过营养敏感靶点雷帕霉素(TOR)途径的氨基酸信号是激活YPP基因表达所必需的。细胞外氨基酸水平的增加，类似于血餐后观察到的增加，是20E刺激YPP基因表达的关键。使用TOR激酶抑制剂雷帕霉素可显著抑制YPP的表达。我们利用RNA干扰来抑制TOR信号通路的两个关键蛋白TOR和结节性硬化症复合体2的表达。TOR的敲除抑制了氨基酸的刺激，而TOR信号的负调控因子结节性硬化症复合体2的敲除导致了YPP表达的增强。因此，基于氨基酸的TOR信号调节血餐后卵发育的激活，这是对蚊子独特生活方式的一种适应。
Mosquitoes generate an enormous burden on human health worldwide. Disease-transmitting species use a reproductive strategy, termed anautogeny, that requires a blood meal to initiate egg maturation. Whereas this strategy is important for driving disease transmission, the molecular mechanisms underlying this phenomenon are still poorly understood. The production of yolk protein precursors (YPPs), a central event in egg maturation, is called vitellogenesis. YPPs are synthesized in the fat body, the insect analogue of the vertebrate liver. Mosquito vitellogenesis is regulated by the steroid hormone 20 hydroxyecdysone (20E). However, 20E alone is not capable of activating vitellogenesis in vivo. Here, we report that amino acid signaling through the nutrient-sensitive target of rapamycin (TOR) pathway is essential for the activation of YPP gene expression. An increase in extracellular amino acid levels, similar to the increase observed after a blood meal, is critical for 20E stimulation of YPP gene expression. Treatment with the TOR kinase inhibitor rapamycin significantly inhibits YPP expression. We used RNA interference to knockdown the expression of two key proteins of the TOR signaling pathway, TOR, and tuberous sclerosis complex 2. Knockdown of TOR inhibited amino acid stimulation while knockdown of tuberous sclerosis complex 2, a negative regulator of TOR signaling, resulted in enhanced YPP expression. Thus, amino acid-based TOR signaling regulates the activation of egg development after a blood meal, an adaptation to the unique life style of mosquitoes.