Department of Entomology, University of California, Riverside, CA 92521.
Institute of Integrative Genome Biology, University of California, Riverside, CA 92521.
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6). doi: 10.1073/pnas.2023470118.
Female mosquitoes feed sequentially on carbohydrates (nectar) and proteins (blood) during each gonadotrophic cycle to become reproductively competent and effective disease vectors. Accordingly, metabolism is synchronized to support this reproductive cyclicity. However, regulatory pathways linking metabolism to reproductive cycles are not fully understood. Two key hormones, juvenile hormone (JH) and ecdysteroids (20-hydroxyecdysone, 20E, is the most active form) govern female mosquito reproduction. genome codes for eight insulin-like peptides (ILPs) that are critical for controlling metabolism. We examined the effects of the JH and 20E pathways on mosquito ILP expression to decipher regulation of metabolism in a reproducing female mosquito. Chromatin immunoprecipitation assays showed genomic interactions between genes and the JH receptor, methoprene-tolerant, a transcription factor, Krüppel homolog 1 (Kr-h1), and two isoforms of the ecdysone response early gene, E74. The luciferase reporter assays showed that Kr-h1 activates , , and , but represses and The 20E pathway displayed the opposite effect in the regulation of E74B repressed and , while E74A activated and Combining RNA interference, CRISPR gene tagging and enzyme-linked immunosorbent assay, we have shown that the JH and 20E regulate protein levels of all eight ILPs. Thus, we have established a regulatory axis between ILPs, JH, and 20E in coordination of metabolism during gonadotrophic cycles of .
雌性蚊子在每个生殖周期中依次进食碳水化合物（花蜜）和蛋白质（血液），从而具备生殖能力并成为有效的疾病传播媒介。相应地，代谢会被同步以支持这种生殖周期性。然而，将代谢与生殖周期联系起来的调节途径尚不完全清楚。两种关键激素，保幼激素（JH）和蜕皮激素（20-羟基蜕皮酮，20E 是最活跃的形式）控制雌性蚊子的繁殖。蚊子基因组编码 8 种胰岛素样肽（ILPs），这些肽对于控制代谢至关重要。我们研究了 JH 和 20E 途径对蚊子 ILP 表达的影响，以破译生殖期雌性蚊子中代谢的调节。染色质免疫沉淀试验表明，基因与 JH 受体 methoprene-tolerant、转录因子 Krüppel 同源物 1（Kr-h1）以及两种蜕皮激素反应早期基因 E74 的同工型之间存在基因组相互作用。荧光素酶报告基因检测表明，Kr-h1 激活 、 、和 ，但抑制 和 。20E 途径在 基因的调节中表现出相反的效果，E74B 抑制 ，而 E74A 激活 。结合 RNA 干扰、CRISPR 基因标记和酶联免疫吸附试验，我们已经表明，JH 和 20E 调节所有 8 种 ILPs 的蛋白水平。因此，我们在生殖周期中建立了一个 ILPs、JH 和 20E 之间的调节轴，以协调代谢。
