MECHANISMS OF OLFACTORY TRANSDUCTION

嗅觉传导机制

• 批准号: 6365363
• 负责人: JOHN H TEETER
• 金额: $ 21.29万
• 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/6365363
• 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）嗅觉在 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的进步， 饮料和幸福感。衰老、疾病、药物和 环境污染物都不利地影响气味的感觉。气味 被鼻子里数以百万计的感觉神经元检测到， 响应特定化学物质刺激的电信号。 气味的识别由多种受体蛋白介导 位于纤毛的膜中，从暴露的末端伸出， 受体神经元气味受体蛋白通过GTP结合 调节蛋白质形成细胞内第二信使， 进而调节膜传导性和电传导的产生， 反应任何将气味剂结合到微胶囊上的步骤的中断， 电反应的产生将导致功能的损害。 气味受体的几个家族和气味受体的许多组分都是由气味受体和气味受体组成的。 转导级联已经通过分子克隆技术鉴定。 然而，受体的功能性表达和匹配特定受体 与其同源气味已被证明是一项艰巨的任务，在哺乳动物， 可能有上千个感受器和数万种气味。鱼回答 对更少的气味剂，并具有数量级更少的气味剂受体。 我们将使用分子和电生理学方法来表征 在原始脊椎动物模型中的嗅觉传导。七鳃鳗似乎 只对几十种气味有反应假设一个相应的限制 气味受体的数量，匹配气味与其 受体大大增加。一些氨基酸气味剂，以及两种 信息素，已确定在这个系统中，和几个cDNA编码 已经分离出了假定的气味受体。一旦全长克隆 获得后，它们将通过在异源系统中表达来表征。的 结果将允许阐明至少一个完整的信号转导 级联反应的受体神经元的脊椎动物，从相互作用的气味与 感受器对动作电位的产生。