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
• 负责人: JINSONG ZHU
• 金额: $ 34.38万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8602831
• 关键词: Adult; Aedes; Affect; Affinity; Alanine; Amino Acid Substitution; Amino Acids; Binding; Biological; Biological Assay; Biological Process; Bite; Blood; Cells; Chemicals; Communicable Diseases; Complex; Culicidae; DNA Binding; Dengue Virus; Development; Disease; Drops; Ecdysterone; Egg Yolk Proteins; Electrophoretic Mobility Shift Assay; Fat Body; Female; Gene Expression; Gene Silencing; Gene Targeting; Genes; Goals; Homology Modeling; Hormone Receptor; Hormones; Hybrids; In Vitro; Incidence; Infection; Ingestion; Insect Hormones; Insect Vectors; Juvenile Hormones; Malaria; Mediating; Methoprene; Modeling; Molecular; Molecular Target; Mosquito Control; Mutagenesis; Mutation; Nucleic Acid Regulatory Sequences; Ovary; Parasites; Persons; Pesticides; Play; Population Control; Production; Property; Protein Binding; Protein Precursors; Proteins; RNA Interference; Recruitment Activity; Reporter; Role; Side; Signal Pathway; Signal Transduction; Structure; Techniques; Testing; Topical application; Transactivation; Transcriptional Activation; Vertebrates; Yeasts; base; chromatin immunoprecipitation; deprivation; design; disease transmission; ecdysteroid receptor; egg; emerging adult; feeding; hormone analog; hormone response element; meetings; novel; pathogen; prevent; promoter; protein protein interaction; receptor; response; steroid hormone; three-dimensional modeling; transcription factor; transmission process; uptake; vector control

DESCRIPTION (provided by applicant): Mosquitoes are insect vectors responsible for the transmission of many infectious diseases to hundreds of millions of people worldwide. Females of most mosquito species require blood from vertebrate animals for their egg development. Multiple bloodfeedings enable mosquitoes to transmit disease pathogens, including malaria parasites and dengue virus, from one person to another. Our long term goal of this project is to elucidate the molecular mechanisms that regulate mosquito egg production and identify target molecules that can be utilized for mosquito control. Mosquito egg development is governed by alternating peaks of two major insect hormones - juvenile hormone (JH) and 20-hydroxyecdysone (20E). Deprivation of JH in newly emerged adult female mosquitoes will halt egg maturation. On the other hand, topical application of JH to mosquitoes shortly after blood feeding interferes with the normal responses to 20E and impairs egg production. We have recently demonstrated that the mosquito Methoprene-tolerant (AaMet) protein is a key player in the juvenile hormone signaling pathway in the newly emerged adult female mosquitoes. AaMet protein binds to JH and forms a complex with AaFISC protein, a coactivator of the 20E receptor. AaMet and AaFISC are found to be associated with the promoters of JH target genes and activate their expression. In addition, our preliminary studies imply that AaMet mediates the inhibitory effects of JH on 20E-induced gene expression. Taken together, the results suggest that AaMet and AaFISC are components of a juvenile hormone receptor. The objective of this project is to elucidate the molecular details of how AaMet functions in juvenile hormone signaling that regulates egg maturation in mosquitoes. In Aim 1, we will perform structure-function studies of the juvenile hormone binding domain in AaMet and define the structural determinants required for high affinity binding to JH. In Aim 2, we will investigate how AaMet and AaFISC proteins are recruited to juvenile hormone response elements in the JH target genes. In Aim 3, we will test the hypothesis that AaMet is involved in the crosstalk between juvenile hormone and 20E signals in blood-fed female mosquitoes. The study will significantly advance our understanding of the molecular action of juvenile hormone in mosquitoes, and provide a structural basis for designing new pesticides that specifically target the mosquito JH signaling pathway.

描述（由申请人提供）：蚊子是昆虫向量，负责将许多传染病传播到全球数亿人。大多数蚊子物种的女性需要脊椎动物的血液来发育。多种血液喂养使蚊子能够从一个人到另一个人传播包括疟疾寄生虫和登革热病毒在内的疾病病原体。我们该项目的长期目标是阐明调节蚊子产生的分子机制，并确定可用于蚊子控制的靶分子。蚊子发育受两种主要昆虫激素的交替峰 - 青少年激素（JH）和20-羟基甲虫（20E）的控制。在新出现的成年雌性蚊子中剥夺JH会停止卵的成熟。另一方面，血液喂养后不久将JH局部应用在蚊子上会干扰对20E的正常反应并损害鸡蛋的产生。我们最近证明，蚊子耐甲酯（AAMET）蛋白是新出现的成年雌性蚊子的少年激素信号通路中的关键参与者。 AAMET蛋白与JH结合，并与20E受体的共激活因子Aafisc蛋白形成复合物。发现AAMET和AAFISC与JH靶基因的启动子相关并激活其表达。此外，我们的初步研究暗示AAMET介导了JH对20E诱导的基因表达的抑制作用。综上所述，结果表明AAMET和AAFISC是青少年激素受体的成分。该项目的目的是阐明AAMET在调节蚊子中卵成熟的青少年激素信号中的作用的分子细节。在AIM 1中，我们将对AAMET中的青少年激素结合结构域进行结构功能研究，并定义高亲和力与JH所需的结构决定因素。在AIM 2中，我们将研究AAMET和AAFISC蛋白如何募集到JH靶基因中的青少年激素反应元件。在AIM 3中，我们将检验以下假设：Aamet参与血液喂养的雌性蚊子中青少年激素和20E信号之间的串扰。这项研究将显着提高我们对蚊子中青少年激素的分子作用的理解，并为设计新的农药提供了专门针对蚊子JH信号途径的新农药的结构基础。