Non-classical roles for opsins in taste and smell

视蛋白在味觉和嗅觉中的非经典作用

• 批准号: 9363622
• 负责人: CRAIG MONTELL
• 金额: $ 41.84万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9363622
• 关键词: Address; Animal Model; Animals; Behavioral Assay; Camphor; Cations; Cells; Cellular biology; Chemicals; Couples; Coupling; Data; Discrimination; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Esthesia; Eye; Family; Family member; Food; Foundations; G-Protein-Coupled Receptors; Goals; Hardness; Homologous Gene; Human; Human Bites; Image; Insecta; Ligands; Light; Liquid substance; Mammals; Modality; Modeling; Molecular Genetics; Neurons; Olfactory Receptor Neurons; Opsin; Organ; Palate; Pathway interactions; Phospholipase C; Phospholipases A; Photoreceptors; Play; Proteins; Receptor Cell; Research; Retina; Retinal; Retinal Pigments; Rhodopsin; Role; Sensory; Sensory Receptors; Shapes; Signal Pathway; Signal Transduction; Smell Perception; Solid; Stimulus; Sucrose; TRP channel; TRPA1 Channel; Taste Buds; Taste Perception; Temperature; Testing; Texture; Tongue; Ursidae Family; Vertebrate Photoreceptors; Viscosity; Vision; Visual system structure; Vitamin A; Work; base; cell type; chromophore; citronellal; experimental study; fly; genetic approach; in vivo; insect disease; insight; member; mutant; olfactory receptor; physical property; prospective; receptor; sensor; sugar; taste system; tool

Abstract The goal of the proposed project is to build on our recent discovery of non-classical roles for opsins in diverse sensory contexts, and specifically to unravel their contributions to the senses of taste and smell. It turns out that opsins, which have been studied for >100 years as light sensors, are expressed outside of the visual system and function in a variety of sensory modalities. Rather than serving exclusively in photosensation, we are finding that opsins are broadly required sensory receptors, potentially playing roles as far-ranging as TRP channels. In mammals, opsins are expressed in a large variety of extra-retinal cell types and organs. However, the extra-ocular roles of these opsins are essentially unexplored. We propose to bring to bear a wide combination of tools available for use in Drosophila to elucidate extra-retinal roles for opsins. The project will employ an extensive suite of in vivo approaches including electrophysiology and Ca2+ imaging, behavioral assays, cell biology and state-of-the art molecular genetic approaches, to study unconventional roles we found for opsins in gustation and olfaction. In addition to the six rhodopsins that are required in the visual system (Rh1-Rh6), flies encode a seventh family member (Rh7). Aim 1 will clarify a light-independent role for Rh7 in the response of gustatory receptor neurons (GRNs) to an aversive tastant. We will test the proposal that Rh7 couples to a signaling cascade that endows GRNs with high sensitivity to the aversive chemical. Aim 2 will investigate a potential role for an opsin in olfaction. Conceptually similar to our recent discovery that opsins expressed in thermosensory neurons allow flies to sense small increases in temperature in the comfortable range, we propose to test that an opsin acts in olfactory receptor neurons to detect minute concentrations of an aversive odorant through an amplification cascade. Aim 3 focuses on illuminating the potential roles of two opsins in the discrimination of foods on the basis of texture. The physical features of food include the viscosity of liquid foods, and the hardness of solid foods. However, the mechanisms underlying food texture sensation are poorly understood. We will investigate the contributions of two opsins to sensing the physical properties of foods. Temperature also influences food palatability. Aim 4 will address the concept that the temperature- dependent change in appeal of sugar-containing foods requires a member of the opsin family. In summary, the proposed project will deepen our understanding of light-independent roles of opsins in gustation and olfaction, and shape the proposal that opsins are broad, polymodal sensors. In view of the wide extra-ocular expression of mammalian opsins, we suggest that this project will provide the conceptual framework for exploring similar roles for opsins in mammals. Finally, taste and smell are critical for insect disease vectors to identify and bite human hosts, and thereby spread diseases that afflict over a billion people annually. Therefore, unraveling highly sensitive receptors for gustation and olfaction in insects has important potential for developing new strategies for interfering with the recognition and attraction of humans by insect disease vectors.

抽象的 拟议项目的目标是建立在我们最近发现的视蛋白在不同的非经典作用的基础上 感官环境，特别是揭示它们对味觉和嗅觉的贡献。事实证明 视蛋白作为光传感器已经被研究了超过 100 年，在视觉之外表达 各种感觉方式的系统和功能。我们不只专注于光感， 发现视蛋白是广泛需要的感觉受体，可能发挥与 TRP 一样广泛的作用 渠道。在哺乳动物中，视蛋白在多种视网膜外细胞类型和器官中表达。然而， 这些视蛋白的眼外作用基本上尚未被探索。我们建议广泛开展 可用于果蝇的工具组合，以阐明视蛋白的视网膜外作用。该项目将 采用广泛的体内方法，包括电生理学和 Ca2+ 成像、行为学 分析、细胞生物学和最先进的分子遗传学方法，来研究我们发现的非常规作用 用于味觉和嗅觉中的视蛋白。除了视觉系统所需的六种视紫红质 (Rh1-Rh6)，果蝇编码第七个家族成员 (Rh7)。目标 1 将阐明 Rh7 在光独立中的作用 味觉受体神经元（GRN）对令人厌恶的促味剂的反应。我们将测试Rh7的提案 与信号级联耦合，赋予 GRN 对令人厌恶的化学物质高度敏感。目标2将 研究视蛋白在嗅觉中的潜在作用。概念上类似于我们最近发现视蛋白 在热感觉神经元中表达，使果蝇能够在舒适的环境中感知温度的微小升高 范围内，我们建议测试视蛋白在嗅觉受体神经元中的作用，以检测视蛋白的微小浓度 通过放大级联消除令人厌恶的气味。目标 3 侧重于阐明两者的潜在角色 视蛋白根据质地辨别食物。食品的物理特性包括粘度 液体食品的硬度和固体食品的硬度。然而，食物质地感觉的机制 人们了解甚少。我们将研究两种视蛋白对感知物理特性的贡献 食物。温度也会影响食物的适口性。目标 4 将阐述温度的概念 含糖食物吸引力的依赖性变化需要视蛋白家族的成员。综上所述， 拟议的项目将加深我们对视蛋白在味觉和嗅觉中与光无关的作用的理解， 并提出了视蛋白是广泛的多模态传感器的建议。鉴于广泛的眼外表达 对于哺乳动物视蛋白，我们建议该项目将为探索类似的 视蛋白在哺乳动物中的作用。最后，味觉和嗅觉对于昆虫病媒识别和叮咬至关重要 人类宿主，从而传播疾病，每年影响超过十亿人。因此，解开 昆虫味觉和嗅觉高度敏感的受体具有开发新受体的重要潜力 昆虫疾病媒介干扰人类识别和吸引的策略。