Department of Entomology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA.
FASEB J. 2012 Mar;26(3):1334-42. doi: 10.1096/fj.11-189969. Epub 2011 Dec 9.
Mosquitoes require blood for egg development, and, as a consequence, they transmit pathogens of devastating diseases. Target of rapamycin (TOR) signaling is a key pathway linking blood feeding and egg development in the mosquito Aedes aegypti. We show that the regulation of the TOR effector translational repressor 4E-BP is finely tuned to the nutritional requirements of the female mosquito, and it occurs at transcriptional and post-translational levels. Immediately after blood feeding, 4E-BP became hyperphosphorylated, suggesting rapid inhibition of its translational repression function. 4E-BP was highly phosphorylated after in vitro incubation of the fat body in the presence of amino acids; this phosphorylation was rapamycin insensitive, in contrast to another TOR target, S6K, phosphorylation of which was rapamycin sensitive. A high level of 4E-BP phosphorylation was also elicited by insulin. Rapamycin and the PI3K inhibitor LY294002 blocked insulin-mediated 4E-BP phosphorylation. RNA-interference depletion of the insulin receptor or Akt resulted in severe reduction of 4E-BP phosphorylation. Phosphorylation and stability of 4E-BP was dependent on its partner eIF4E translation initiation factor. Silencing of 4E-BP resulted in reduction of the life span of adult female mosquitoes. This study demonstrates a dual nutritional and hormonal control of 4E-BP and its role in mosquito egg development.
蚊子的卵发育需要血液，因此它们传播具有破坏性疾病的病原体。雷帕霉素靶蛋白 (TOR) 信号通路是连接蚊子 Aedes aegypti 吸血和卵发育的关键途径。我们表明，TOR 效应器翻译抑制剂 4E-BP 的调节精细地适应雌性蚊子的营养需求，并且它发生在转录和翻译后水平。在吸血后立即，4E-BP 被高度磷酸化，表明其翻译抑制功能迅速被抑制。在存在氨基酸的情况下，脂肪体在体外孵育后，4E-BP 高度磷酸化；与另一个 TOR 靶标 S6K 不同，其磷酸化对雷帕霉素敏感。胰岛素也能引起 4E-BP 的高水平磷酸化。雷帕霉素和 PI3K 抑制剂 LY294002 阻断了胰岛素介导的 4E-BP 磷酸化。胰岛素受体或 Akt 的 RNA 干扰消耗导致 4E-BP 磷酸化严重减少。4E-BP 的磷酸化和稳定性取决于其伴侣 eIF4E 翻译起始因子。沉默 4E-BP 会导致成年雌性蚊子寿命缩短。本研究证明了 4E-BP 的双重营养和激素控制及其在蚊子卵发育中的作用。
