Cytochrome P450 G subfamily member as a putativeodor

细胞色素 P450 G 亚家族成员作为假定的气味

• 批准号: 10194525
• 负责人: Monika Gulia-Nuss
• 金额: $ 24.11万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-05 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194525
• 关键词: Acute; Adult; Aedes; Alcohols; Aldehydes; Animals; Behavior; Biochemistry; Blood; Chemicals; Communicable Diseases; Culicidae; Cytochrome P450; Cytochromes; Data; Enzymes; Female; Head; Insecta; Insecticide Resistance; Insecticides; Knock-out; Literature; Maxilla; Messenger RNA; Molecular Biology; Mosquito Control; Mosquito-borne infectious disease; Neurosciences; Neurosecretory Systems; Nutrient; Odors; Olfactory Pathways; Orthologous Gene; Partner in relationship; Peripheral; Plants; Play; Process; Production; RNA Interference; Role; Signal Transduction; Smell Perception; Source; System; Techniques; Testing; Tissues; Work; Yellow Fever; base; egg; enzyme substrate; human disease; improved; information processing; knock-down; member; novel; vector mosquito

Female mosquitoes are vectors for some of the most debilitating infectious diseases of humans. Current chemical management strategies use insecticides that target the neuro-endocrine system almost exclusively. With insecticide resistance on the rise, there is a serious resurgence of mosquito-borne diseases, and therefore an urgent need to develop new targets for new strategies. Female of most mosquito species require vertebrate blood to provide nutrients for egg production and therefore need to locate an appropriate host mainly through their sense of smell. Consequently, mosquitoes have evolved an acute olfactory information processing system that detects and processes odor information to enable localizing the odor source, and finally rapidly inactivates the odor signal so as to maintain high odor sensitivity. Studies in the last several decades have greatly improved our understanding of how odors are detected and processed by the olfactory circuit, the neuroscience underlying odor-signal inactivation is poorly understood. Recent studies have suggested that antennal cytochrome P450s (CYPs) play an important role in odor molecule breakdown. In honeybees, a member of insect-specific CYP subfamily, CYP4G11, has been shown to degrade short-chain alcohols and aldehydes (common volatile odor molecules in plants and animal odor). The yellow fever mosquito, Aedes aegypti, has two functional CYP4G orthologs, CYP4G35 and CYP4G36. Our preliminary data show that CYP4G35 mRNA levels are highest in the head and peripheral olfactory tissues (antennae, maxillary palps, proboscis, and head). CYP4G35 knockdown by RNAi results in vertebrate host avoidance by the adults. Based on the evidence in the literature and our preliminary data, we hypothesize that the CYP4G35 is an odor degrading enzyme, important for odor clearance. We will test this hypothesis through two specific aims: Aim 1) assessing the effects of CYP4G35 knockout on host and mate finding (olfaction and mating), and Aim 2) Functional determination of CYP4G35 as an odor degrading enzyme by determining enzyme substrates and localization in the antennae. We will employ techniques in molecular biology, biochemistry, and neuroscience/behavior to achieve these aims. This work will impact the field by providing 1) a novel target for mosquito control, and 2) an enhanced understanding of the olfactory information processing in mosquitoes.

雌性蚊子是一些最能使人衰弱的传染病的媒介。 目前的化学品管理战略使用的杀虫剂几乎都是针对神经内分泌系统的 独家。随着杀虫剂耐药性的上升，蚊媒疾病严重死灰复燃， 因此迫切需要为新战略制定新目标。 大多数蚊子物种的雌性需要脊椎动物的血液来为产卵提供营养， 因此主要需要通过嗅觉来定位合适的宿主。因此，蚊子 已经进化出一种急性嗅觉信息处理系统，其检测并处理气味信息， 能够定位气味源，并最终快速灭活气味信号，以保持高气味 灵敏度过去几十年的研究极大地提高了我们对气味的理解， 嗅觉回路检测和处理气味信号，神经科学的基础气味信号失活是很差的 明白 最近的研究表明，触角细胞色素P450（CYP）在嗅觉中起着重要作用 分子分解在蜜蜂中，昆虫特异性的CYP 4G 11亚家族的一个成员已经被证明是 降解短链醇和醛（植物和动物气味中常见的挥发性气味分子）。 黄热病蚊子，埃及伊蚊，有两个功能性CYP 4G直系同源物，CYP 4G 35和CYP 4G 36。 我们的初步数据显示，CYP 4G 35 mRNA水平在头部和外周嗅觉组织中最高 （触角、下颚须、长鼻和头部）。通过RNAi敲低CYP 4G 35导致脊椎动物宿主 成年人的回避。根据文献中的证据和我们的初步数据，我们假设 CYP 4G 35是一种气味降解酶，对于气味清除很重要。我们将测试这个 通过两个特定的目的来研究这一假说：目的1）评估CYP 4G 35基因敲除对宿主和配偶的影响 发现（嗅觉和交配）和目的2）确定CYP 4G 35作为气味降解酶的功能 通过确定酶底物和在触角中的定位。我们将采用分子技术 生物学、生物化学和神经科学/行为来实现这些目标。 这项工作将通过以下方式影响该领域：1）蚊子控制的新目标，以及2）增强的 了解蚊子的嗅觉信息处理。