MECHANISMS OF OLFACTORY TRANSDUCTION

嗅觉传导机制

• 批准号: 6616657
• 负责人: JOHN H TEETER
• 金额: $ 23.64万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6616657
• 关键词: Agnatha; Xenopus; Xenopus oocyte; action potentials; biological signal transduction; chemoreceptors; complementary DNA; gene expression; genetic library; genetic screening; in situ hybridization; molecular cloning; neurons; northern blottings; nucleic acid sequence; odors; olfactory stimulus; protein localization; receptor; receptor binding; second messengers; tissue /cell preparation; voltage /patch clamp

DESCRIPTION: (provided by applicant) The significance of olfaction in maintaining our overall quality of life is becoming increasingly appreciated with advances in our understanding of how odors influence the enjoyment of food and beverages and our sense of well-being. Aging, disease, drugs and environmental pollutants all adversely affect the perception of odors. Odors are detected by millions of sensory neurons in the nose that generate an electrical signal in response to stimulation by particular chemicals. Recognition of odors is mediated by a large variety of receptor proteins located in the membranes of cilia projecting from the exposed ends of the receptor neurons. Odorant receptor proteins are linked by GTP-binding regulatory proteins to the formation of intracellular second messengers, which in turn modulate membrane conductance and the generation of an electrical response. Disruption of any of the steps coupling odorant binding to the generation of the electrical response would result in impairment of function. Several families of odorant receptors and many of the components of the transduction cascade have been identified by molecular cloning techniques. However, functional expression of receptors and matching a particular receptor with its cognate odorants have proven a daunting task in mammals, where there are perhaps thousand receptors and tens of thousands of odorants. Fish respond to many fewer odorants and have an order of magnitude fewer odorant receptors. We will use molecular and electrophysiological approaches to characterize olfactory transduction in a primitive vertebrate model. Sea lampreys appear to respond to only a few dozen odorants. Assuming a correspondingly restricted number of odorant receptors, the probability of matching an odorant with its receptor is greatly increased. A few amino acid odorants, as well as two pheromones, have been identified in this system, and several cDNAs encoding presumed odorant receptors have been isolated. Once full-length clones are obtained, they will be characterized by expression in heterologous systems. The results will allow elucidation of at least one complete signal transduction cascade in receptor neurons of a vertebrate, from interaction of odorant with a receptor to the generation of action potentials.

描述：（由申请人提供）嗅觉的重要性 保持我们的整体生活质量越来越受到重视 随着我们对气味如何影响食物享受的理解不断深入 和饮料以及我们的幸福感。衰老、疾病、药物和 环境污染物都会对气味的感知产生不利影响。气味 鼻子中数以百万计的感觉神经元检测到这些神经元，这些神经元产生 响应特定化学物质刺激的电信号。 气味的识别是由多种受体蛋白介导的 位于从纤毛暴露端突出的纤毛膜中 受体神经元。气味受体蛋白通过 GTP 结合连接 细胞内第二信使形成的调节蛋白， 反过来调节膜电导并产生电 回复。任何将气味剂与物质结合的步骤被破坏 电反应的产生将导致功能受损。 气味受体的几个家族和气味受体的许多成分 转导级联已通过分子克隆技术鉴定。 然而，受体的功能表达和特定受体的匹配 事实证明，对于哺乳动物来说，其同源气味是一项艰巨的任务， 也许有数千个受体和数以万计的气味剂。鱼有反应 气味物质少得多，气味受体也少一个数量级。 我们将使用分子和电生理学方法来表征 原始脊椎动物模型中的嗅觉转导。海七鳃鳗似乎 仅对几十种气味剂有反应。假设有相应的限制 气味受体的数量，气味与其匹配的概率 受体大大增加。一些氨基酸气味剂，以及两种 已在该系统中鉴定出信息素，以及编码的几个 cDNA 推测的气味受体已被分离出来。一旦全长克隆被 获得后，它们的特征在于在异源系统中的表达。这 结果将能够阐明至少一种完整的信号转导 脊椎动物受体神经元中的级联反应，来自气味剂与气味的相互作用 产生动作电位的受体。