Illuminating the structure and function of Type I taste cells

阐明 I 型味觉细胞的结构和功能

• 批准号: 10049240
• 负责人: Sue C. Kinnamon
• 金额: $ 50.45万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10049240
• 关键词: ATP Receptors; Address; Affect; Amiloride; Anatomy; Apical; Astrocytes; Brain Stem; Calcium; Cell physiology; Cells; Cellular Morphology; Cre driver; Data; Detection; Development; Eating; Enzymes; Event; Fiber; Food; Fungiform Papilla; G-Protein-Coupled Receptors; GABA Antagonists; GABA transporter; GLAST Protein; Glutamates; Halorhodopsins; Lead; Light; LoxP-flanked allele; Mediating; Mediator of activation protein; Membrane; Membrane Transport Proteins; Molecular; Monitor; Morphology; Mus; NTPDase2; Nature; Nerve; Nerve Fibers; Nervous system structure; Neuroglia; Neurotransmitters; Nutritional; Obesity; Oral; Oral cavity; Oxytocin; P2X-receptor; Pharmacologic Substance; Play; Poison; Process; Receptor Cell; Reporter; Reporting; Role; Sampling; Scanning; Sensory; Serotonin; Signal Transduction; Sodium; Sodium Chloride; Structure; Structure of gustatory pore; Substance P; Synapses; Taste Buds; Taste Perception; Testing; Tomatoes; Tongue; Toxic effect; Transgenic Mice; Trigeminal System; Type I Epithelial Receptor Cell; Type II Epithelial Receptor Cell; Type III Epithelial Receptor Cell; afferent nerve; cell type; chorda tympani; epithelial Na+ channel; experimental study; gamma-Aminobutyric Acid; intercellular communication; neurotransmitter release; patch clamp; presynaptic; rat Gnat3 protein; receptor; reconstruction; response; salt sensitive; sensor; taste stimuli; taste system; taste transduction; tool; transmission process; uptake

Abstract Taste buds are multicellular sensors reporting taste, which reflects quality and potential toxicity for potential food items. Two of the 3 cell types (Type II and Type III) comprising a taste bud are well described in terms of molecular features for transduction and transmission of different taste qualities whereas Type I cells are described as being supporting or glial-like. In this proposal we test the hypothesis that Type I taste cells serve two critical functions. First, our preliminary reconstructions of taste buds show that Type I cells completely surround and separate other cell types in a taste bud; thus Type I cells must be important for signaling and integration of taste information within the bud. Second, our ultrastructural analysis further shows that some Type I cells extend an apical process through the taste pore to sample the oral contents and so may transduce some components of salty taste. We propose to use correlated anatomical, functional and molecular means to classify and characterize Type I cells in taste buds from mice. The first set of experiments will extend our preliminary analysis of Type I cells in circumvallate taste buds to test whether Type I cells in fungiform taste buds similarly separate Type II and Type III cells from one another. Further we test whether the Type I cells participate in intrabud signaling by releasing GABA or other neurotransmitters in response to the ATP released by stimulated Type II (sweet-bitter-umami) cells. The GABA can then act on adjacent Type II cells to terminate signaling and reduce subsequent responsiveness to tastants. In Aim 2, we test whether any morphological subtype of Type I cells expresses functional amiloride-sensitive salt (ENaC) receptors and if so, determine the relationship of these cells to sensory nerve fibers. Conventional EM indicates that Type I cells do not form synapses leaving open the question of how any Type I cell response could be communicated to the nervous system. We suggest that Type I cells, like glial cells in the CNS, can release neurotransmitter by reversal of membrane transporters for GABA or glutamate or opening of large pore channels. In the end we will have resolved two important questions in transduction and transmission of taste information by defining the nature of intrabud signaling between receptor cell types, and secondly finally determining the identity of cells underlying amiloride-sensitive salt transduction.

抽象的 味蕾是报告味道的多细胞传感器，反映了潜在的质量和潜在毒性 食品。构成味蕾的 3 种细胞类型（II 型和 III 型）中的两种在以下方面得到了很好的描述： 不同味觉品质转导和传递的分子特征，而 I 型细胞则 被描述为支持性或神经胶质样。在这个提案中，我们测试了 I 型味觉细胞服务的假设 两个关键功能。首先，我们对味蕾的初步重建表明，I型细胞完全 包围并分隔味蕾中的其他细胞类型；因此，I 型细胞对于信号传导和 味觉信息在芽内的整合。其次，我们的超微结构分析进一步表明，一些 I 型细胞通过味孔延伸顶端过程以采样口腔内容物，因此可能转导 一些咸味成分。我们建议使用相关的解剖学、功能性和分子手段来 对小鼠味蕾中的 I 型细胞进行分类和表征。第一组实验将扩展我们的 初步分析周围味蕾的I型细胞以测试I型细胞是否具有菌状味觉 芽同样将 II 型和 III 型细胞彼此分开。我们进一步测试 I 型细胞是否 通过响应释放的 ATP 释放 GABA 或其他神经递质来参与芽内信号传导 通过刺激 II 型（甜苦鲜味）细胞。然后 GABA 可以作用于相邻的 II 型细胞以终止 信号传导并降低随后对促味剂的反应。在目标 2 中，我们测试是否有任何形态学 I 型细胞的亚型表达功能性阿米洛利敏感盐 (ENaC) 受体，如果是这样，请确定 这些细胞与感觉神经纤维的关系。常规 EM 表明 I 型细胞不形成 突触留下了一个悬而未决的问题，即任何 I 型细胞反应如何传递给神经 系统。我们认为 I 型细胞，如中枢神经系统中的神经胶质细胞，可以通过逆转 GABA 或谷氨酸的膜转运蛋白或大孔通道的开放。最终我们将会有 通过定义味觉信息的本质解决了味觉信息转导和传递中的两个重要问题 受体细胞类型之间的芽内信号传导，其次最终确定潜在细胞的身份 阿米洛利敏感的盐转导。