Molecular Genetic Investigation of Taste Sensation

摘要 从昆虫到哺乳动物的动物都使用特定的味觉受体来感知不同的食物风味， 如甜、苦、酸和咸。与其他基本味觉形态相反，咸味和酸味是 主要分别通过钠和质子离子通道介导。动物通常喜欢低水平的 盐或酸，并拒绝高浓度。由于盐和酸是重要的矿物质营养素， 过量食用盐或酸会导致肠胃，代谢和心血管疾病。 虽然咸味和酸味对人类健康有着深远的影响，但咸味和酸味的分子特性仍然是一个问题。 酸味受体还没有完全确定。此外，咸味背后的神经回路 反应和摄入量未知。我们以果蝇为模式生物， 先前的工作鉴定了一种新的离子型谷氨酸受体，其是高盐感觉所必需的。 此外，我们发现，苍蝇大脑中的一小部分神经元调节高盐回避。此外，委员会还认为， 我们发现，一种新的离子通道，它可以直接被质子激活，是需要有吸引力的 果蝇的酸味反应 基于我们的初步发现，我们建议使用果蝇作为模式生物来探索 咸味和酸味感知的分子和神经机制。特别是，我们将追求两个主要的 调查路线：（1）破译咸味感觉的分子和神经机制;（2）破译 酸味感觉的分子基础鉴于盐和酸的味觉传导机制是 类似于苍蝇和哺乳动物，我们从果蝇研究中收集到的分子见解将 为包括人类在内的哺乳动物的咸和酸味觉研究提供了信息。

Abstract Animals ranging from insects to mammals employ specific taste receptors to perceive distinct food flavors, such as sweet, bitter, sour, and salty. In contrast to other basic taste modalities, salty and sour tastes are primarily mediated through sodium and proton ion channels, respectively. Animals normally prefer low levels of salt or acid and reject high concentrations. Since salt and acid are important mineral nutrients, insufficient or excessive consumption of salt or acid can lead to gastrointestinal, metabolic, and cardiovascular diseases. Although salty and sour tastes have a profound impact on human health, the molecular identities of salty and sour taste receptors have not been fully determined. In addition, the neuronal circuits underlying salt taste response and intake are unknown. Using the fruit fly, Drosophila melanogaster, as a model organism, our previous work identified a new ionotropic glutamate receptor that is required for high-salt sensation. Additionally, we found that a small subset of neurons in the fly brain regulate high-salt avoidance. Moreover, we discovered that a novel ion channel, which can be directly activated by protons, is required for the attractive sour taste response in flies. Building on our preliminary findings, we propose to use the fruit fly as a model organism to explore the molecular and neural mechanisms of salty and sour taste perception. In particular, we will pursue two principal lines of inquiry: (1) decipher the molecular and neural mechanisms of salty taste sensation; and (2) decipher the molecular basis of sour taste sensation. Given that taste transduction mechanisms to salt and acid are analogous between flies and mammals, the molecular insights gleaned from our research in fruit flies will inform studies of salty and sour taste sensations in mammals, including humans.