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.

雌性蚊子是人类一些最严重的传染病的媒介。 目前的化学管理策略使用几乎针对神经内分泌系统的杀虫剂 只。随着杀虫剂抗药性的增强，蚊媒疾病重新抬头， 因此迫切需要为新战略制定新目标。 大多数蚊子种类的雌性需要脊椎动物的血液来为产卵和提供营养。 因此需要主要通过嗅觉来寻找合适的宿主。因此，蚊子 已经进化出一种敏锐的嗅觉信息处理系统，可以检测和处理气味信息 能够定位气味源，最终快速灭活气味信号，维持高气味 敏感性。过去几十年的研究极大地提高了我们对气味如何产生的理解。 由嗅觉回路检测和处理，气味信号失活的神经科学基础很差 明白了。 最近的研究表明触角细胞色素 P450s (CYPs) 在气味中发挥着重要作用 分子分解。在蜜蜂中，昆虫特异性 CYP 亚家族的成员 CYP4G11 已被证明 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具有两种功能性 CYP4G 直系同源物：CYP4G35 和 CYP4G36。 我们的初步数据显示，CYP4G35 mRNA 水平在头部和周围嗅觉组织中最高 （触角、上颌须、长鼻和头部）。 RNAi 敲低脊椎动物宿主体内的 CYP4G35 大人的回避。根据文献证据和我们的初步数据，我们假设 CYP4G35 是一种气味降解酶，对于清除气味很重要。我们将测试这个 通过两个具体目标提出假设： 目标 1) 评估 CYP4G35 敲除对宿主和配偶的影响 发现（嗅觉和交配），以及目标 2) CYP4G35 作为气味降解酶的功能测定 通过确定酶底物和触角的定位。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。 这项工作将通过提供 1）一个新的蚊子控制目标，以及 2）一个增强的方法来影响该领域。 了解蚊子的嗅觉信息处理。