Electrophysiological basis of sour taste transduction

描述（由申请人提供）：大多数脊椎动物对五种基本味道有反应：甜、苦、鲜、酸和咸，每一种味道都提供了摄入食物的营养成分和安全性的独特信息。五种味觉品质中的每一种都是由舌头和上颚上皮味蕾中发现的味觉受体细胞的不同子集检测到的。虽然在理解调节苦味、甜味和鲜味的分子和机制方面已经取得了很大的进展，但对酸味的电生理基础却知之甚少。检测酸味的细胞可以通过TRP离子通道PKD2L1的表达来识别，而PKD2L1本身并不是酸味所必需的。在最近的工作中，我们使用Pkd2l1启动子驱动黄色荧光蛋白（YFP）的小鼠，我们发现酸味细胞具有以前未被表征的质子电导，该电导位于细胞顶端，并在响应细胞外酸化时携带向内电流。这使我们提出了一个模型，其中质子通过质子通道进入使细胞去极化，导致动作电位和递质释放。此外，质子进入可能导致细胞质酸化，这可能作用于静止的K+通道，进一步使细胞去极化。这个过程可以在多个步骤中进行调节，使系统能够适应不同的条件和生物体的需要。目前的建议包括三个具体目标，利用这些新产生的转基因小鼠系和转录组分析的最新结果来测试该模型并进一步阐明酸转导的机制。味觉是人类和其他生物调节其摄食行为的重要方式，因此味觉信号传导机制的识别可以直接影响人类的健康和福祉。

DESCRIPTION (provided by applicant): Most vertebrate species are responsive to five basic tastes: sweet, bitter, umami, sour and salty, each of which provides unique information on the nutritional content and safety of ingested food. Each of the five taste qualities is detected by a distinct subset of taste receptor cells found in taste buds on the tongue and the palate epithelium. While great strides have been made in understanding the molecules and mechanisms that mediate bitter, sweet, and umami tastes, relatively little is known about the electrophysiological basis for sour taste. The cells that detect sour taste can be identified by expression of the TRP ion channel PKD2L1, which itself is not necessary for sour taste. In recent work, using a mouse in which yellow fluorescent protein (YFP) was driven by the promoter of Pkd2l1, we showed that sour taste cells have a previously uncharacterized proton conductance which is apically located and carries an inward current in response to extracellular acidification. This has led us to propose a model in which proton entry through the proton channel depolarizes the cells leading to action potentials and transmitter release. In addition, proton entry may cause cytosolic acidification, which could act on resting K+ channels to further depolarize the cells. This process may be subject to modulation at multiple steps, allowing the system to adapt to varying conditions and needs of the organism. The present proposal include three specific aims that take advantage of these newly generated transgenic mouse lines and recent results from transcriptome profiling to test this model and to further elucidate mechanisms of sour transduction. Taste is an essential way in which humans and other organisms regulate their ingestive behavior and the identification of mechanisms of taste signaling can therefore have a direct impact on human health and well-being.