Department of Entomology, University of Georgia, Athens, GA 30602, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Insect Biochem Mol Biol. 2013 Dec;43(12):1100-8. doi: 10.1016/j.ibmb.2013.09.004. Epub 2013 Sep 26.
Most mosquito species must feed on the blood of a vertebrate host to produce eggs. In the yellow fever mosquito, Aedes aegypti, blood feeding triggers medial neurosecretory cells in the brain to release insulin-like peptides (ILPs) and ovary ecdysteroidogenic hormone (OEH). Theses hormones thereafter directly induce the ovaries to produce ecdysteroid hormone (ECD), which activates the synthesis of yolk proteins in the fat body for uptake by oocytes. ILP3 stimulates ECD production by binding to the mosquito insulin receptor (MIR). In contrast, little is known about the mode of action of OEH, which is a member of a neuropeptide family called neuroparsin. Here we report that OEH is the only neuroparsin family member present in the Ae. aegypti genome and that other mosquitoes also encode only one neuroparsin gene. Immunoblotting experiments suggested that the full-length form of the peptide, which we call long OEH (lOEH), is processed into short OEH (sOEH). The importance of processing, however, remained unclear because a recombinant form of lOEH (rlOEH) and synthetic sOEH exhibited very similar biological activity. A series of experiments indicated that neither rlOEH nor sOEH bound to ILP3 or the MIR. Signaling studies further showed that ILP3 activated the MIR but rlOEH did not, yet both neuropeptides activated Akt, which is a marker for insulin pathway signaling. Our results also indicated that activation of TOR signaling in the ovaries required co-stimulation by amino acids and either ILP3 or rlOEH. Overall, we conclude that OEH activates the insulin signaling pathway independently of the MIR, and that insulin and TOR signaling in the ovaries is coupled.
大多数蚊子物种必须以脊椎动物宿主的血液为食才能产卵。在黄热病蚊子（Aedes aegypti）中，血液摄取会触发脑中的中脑神经分泌细胞释放胰岛素样肽（ILP）和卵巢蜕皮激素生成激素（OEH）。这些激素随后直接诱导卵巢产生蜕皮激素（ECD），激活脂肪体中卵黄蛋白的合成以供卵母细胞摄取。ILP3 通过与蚊子胰岛素受体（MIR）结合来刺激 ECD 的产生。相比之下，关于 OEH 的作用模式知之甚少，它是一种称为神经副蛋白的神经肽家族的成员。在这里，我们报告 OEH 是 Ae. aegypti 基因组中唯一存在的神经副蛋白家族成员，而其他蚊子也只编码一个神经副蛋白基因。免疫印迹实验表明，该肽的全长形式，我们称之为长 OEH（lOEH），被加工成短 OEH（sOEH）。然而，由于重组形式的 lOEH（rlOEH）和合成的 sOEH 表现出非常相似的生物学活性，因此处理的重要性仍不清楚。一系列实验表明，rlOEH 和 sOEH 均不与 ILP3 或 MIR 结合。信号研究进一步表明，ILP3 激活了 MIR，但 rlOEH 没有，尽管这两种神经肽都激活了 Akt，Akt 是胰岛素途径信号的标志物。我们的结果还表明，卵巢中 TOR 信号的激活需要氨基酸和 ILP3 或 rlOEH 的共同刺激。总的来说，我们得出的结论是，OEH 独立于 MIR 激活胰岛素信号通路，并且卵巢中的胰岛素和 TOR 信号是耦合的。
