Molecular Genetic Investigation of Taste Sensation

摘要 从昆虫到哺乳动物，各种动物都使用特定的味觉感受器来感知不同的食物味道， 如甜的、苦的、酸的和咸的。与其他基本口味不同，咸味和酸味是 主要分别通过钠离子通道和质子离子通道介导。动物通常更喜欢低水平的 盐或酸，拒绝高浓度。由于盐和酸是重要的矿物质营养物质，不足或 过量摄入盐或酸会导致胃肠道、代谢和心血管疾病。 虽然咸味和酸味对人类健康有深远的影响，但咸味和酸味的分子特性 酸味感受器还没有完全确定。此外，盐味背后的神经元回路 反应和摄入量尚不清楚。使用果蝇，果蝇，作为一个模式生物，我们的 以前的工作发现了一种新的离子型谷氨酸受体，这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着高盐的避免。此外， 我们发现，一种新的离子通道，可以被质子直接激活，是吸引人的 果蝇对酸味的反应。 根据我们的初步发现，我们建议以果蝇作为模式生物来探索 咸味和酸味知觉的分子和神经机制。特别是，我们将追求两个原则 研究思路：(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。鉴于味觉对盐和酸的转导机制是 类似于苍蝇和哺乳动物，从我们对果蝇的研究中收集的分子洞察力将 为包括人类在内的哺乳动物的咸味和酸味的研究提供信息。

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.