Molecular mechanism of juvenile hormone action in mosquito reproduction

保幼激素在蚊子繁殖中作用的分子机制

基本信息

  • 批准号:
    10373049
  • 负责人:
  • 金额:
    $ 40.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-02-01 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

Project Summary Mosquitoes are responsible for the transmission of many infectious diseases such as malaria, dengue fever, and Zika virus. Vector control using insecticides is currently the primary means of preventing the transmission of these diseases. In light of the rapid spread of insecticide resistance in mosquito populations, it is imperative to add new insecticides with different modes of action to the arsenal of mosquito control agents. The juvenile hormone (JH) signaling pathway is an attractive target for the control of mosquito vectors. JH is a key regulator of mosquito development and reproduction. Exposure of adult mosquitoes to pyriproxyfen, a synthetic JH mimic, has shown promise to effectively sterilize female mosquitoes. Our goal of this project is to elucidate the molecular pathways utilized by JH and its mimics to modulate mosquito fecundity. Mosquito egg development is mainly governed by JH and 20-hydroxyecdysone (20E). In the last funding cycle, we demonstrated that the Methoprene-tolerant (MET) protein is an intracellular receptor of JH. Both natural JH and pyriproxyfen binds to Aedes aegypti MET with high affinity. Upon binding of JH, MET forms a dimer with Taiman, a transcriptional factor that is involved in both JH and 20E responses. The MET-Taiman complex directly regulates the expression of JH-controlled genes. Besides the genomic action, we also reported a rapid JH signaling that is initiated from the plasma membrane. The non-genomic action, which relies on receptor tyrosine kinases (RTK), modulates the DNA-binding of the MET-Taiman complex and regulates the alternative splicing of the taiman gene. While the membrane-initiated JH signaling plays critically important roles in mosquito reproduction, the membrane JH receptor and the specific RTK have not yet been identified in mosquitoes. Our recent study demonstrates that a small portion of MET is associated with the plasma membrane in mosquito cells. Furthermore, depletion of MET eradicates the JH-activated increase in intracellular Ca2+, which is part of extranuclear JH signaling. Thus, our results suggest that the membrane- associated MET acts as a membrane JH receptor to mediate the non-genomic action of JH. In this proposed study, we will test the hypothesis that the JH action in mosquitoes is mediated by both membrane-bound and nuclear MET proteins, and that pyriproxyfen uses this JH signaling pathway to inhibit 20E-regulated gene expression. In Aim 1, we will define the roles of membrane MET in the membrane binding of JH and the membrane-initiated JH signaling. In Aim 2, we will investigate how membrane MET mediates the nongenomic action of JH in mosquitoes. In Aim 3, we will elucidate how pyriproxyfen utilizes the JH signaling pathway to suppress the vitellogenic 20E response. This study will add a new dimension to our understanding of the JH signaling pathway that is required for mosquito reproduction. It may also reveal new targets in the JH signaling pathway that can be exploited for pesticide development.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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JINSONG ZHU其他文献

JINSONG ZHU的其他文献

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{{ truncateString('JINSONG ZHU', 18)}}的其他基金

Juvenile hormone action, and crosstalk between juvenile hormone and 20-hydroxyecd
保幼激素的作用以及保幼激素与 20-羟基ecd 之间的串扰
  • 批准号:
    8789771
  • 财政年份:
    2012
  • 资助金额:
    $ 40.36万
  • 项目类别:
Juvenile hormone action, and crosstalk between juvenile hormone and 20-hydroxyecd
保幼激素的作用以及保幼激素与 20-羟基ecd 之间的串扰
  • 批准号:
    8415499
  • 财政年份:
    2012
  • 资助金额:
    $ 40.36万
  • 项目类别:
Juvenile hormone action, and crosstalk between juvenile hormone and 20-hydroxyecd
保幼激素的作用以及保幼激素与 20-羟基ecd 之间的串扰
  • 批准号:
    8602831
  • 财政年份:
    2012
  • 资助金额:
    $ 40.36万
  • 项目类别:
Molecular mechanism of juvenile hormone action in mosquito reproduction
保幼激素在蚊子繁殖中作用的分子机制
  • 批准号:
    10579247
  • 财政年份:
    2012
  • 资助金额:
    $ 40.36万
  • 项目类别:
Juvenile hormone action, and crosstalk between juvenile hormone and 20-hydroxyecd
保幼激素的作用以及保幼激素与 20-羟基ecd 之间的串扰
  • 批准号:
    8272970
  • 财政年份:
    2012
  • 资助金额:
    $ 40.36万
  • 项目类别:
Experimental identification of microRNA targets in mosquitoes during Plasmodium i
蚊子疟原虫 i 期 microRNA 靶标的实验鉴定
  • 批准号:
    8302208
  • 财政年份:
    2011
  • 资助金额:
    $ 40.36万
  • 项目类别:
Experimental identification of microRNA targets in mosquitoes during Plasmodium i
蚊子疟原虫 i 期 microRNA 靶标的实验鉴定
  • 批准号:
    8095042
  • 财政年份:
    2011
  • 资助金额:
    $ 40.36万
  • 项目类别:
Translational Regulation of Mosquito mRNAs during Plasmodium Infection
疟原虫感染期间蚊子 mRNA 的翻译调控
  • 批准号:
    7911661
  • 财政年份:
    2009
  • 资助金额:
    $ 40.36万
  • 项目类别:
Translational Regulation of Mosquito mRNAs during Plasmodium Infection
疟原虫感染期间蚊子 mRNA 的翻译调控
  • 批准号:
    7739063
  • 财政年份:
    2009
  • 资助金额:
    $ 40.36万
  • 项目类别:

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