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: 10292443
• 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/10292443
• 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; antagonist; 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 味蕾是多细胞传感器报告味道，它反映了潜在的质量和潜在毒性 食品。包括味蕾的3种细胞类型中的两种（II型和III型）在 用于转导和传播不同味道质量的分子特征，而I型细胞是 被描述为支持或类似神经胶质。在此提案中，我们检验了I型味道单元使用的假设 两个关键功能。首先，我们的味蕾初步重建显示了I型细胞 在味蕾中包围和分开其他细胞类型；因此，I型单元必须对于信号传导和 芽中的味觉信息的整合。其次，我们的超微结构分析进一步表明 I型细胞通过味道孔扩展了顶端过程，以采样口服含量，因此可能会导致 一些咸味的成分。我们建议使用相关的解剖，功能和分子手段 对小鼠的味蕾进行分类和表征I型细胞。第一组实验将扩展我们的 对I型细胞的初步分析，以绕过味蕾，以测试I型细胞中的I型细胞是否味觉味觉 芽类似地将II型和III型细胞彼此分开。此外，我们测试I型单元是否 通过释放GABA或其他神经递质来响应ATP，参与内部信号传导 通过刺激的II型（甜腹部 - 乌玛）细胞。然后，GABA可以作用于相邻的II型细胞以终止 发出信号并降低随后对葡萄酒的反应性。在AIM 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，请确定 这些细胞与感觉神经纤维的关系。常规EM表示I型单元不形成 突触留下了一个问题，即如何将任何类型的细胞响应传达给神经 系统。我们建议I型细胞，例如中枢神经系统中的神经胶质细胞，可以通过逆转释放神经递质 用于GABA或谷氨酸的膜转运蛋白或大孔通道的开口。最后，我们将有 通过定义的性质，解决了在转导和传输口味信息方面的两个重要问题 受体细胞类型之间的内部信号传导，其次最终确定了基础细胞的身份 阿米洛里德敏感的盐转导。