MECHANISMS OF OLFACTORY TRANSDUCTION

描述：(申请人提供)嗅觉在儿童中的意义 保持我们的整体生活质量变得越来越受重视 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 是由鼻子中数以百万计的感觉神经元检测到的，这些神经元产生了 对特定化学物质的刺激作出反应的电信号。 气味的识别是由多种受体蛋白介导的。 位于纤毛膜中，从裸露的末端伸出 感受器神经元。气味受体蛋白通过GTP结合连接在一起 调节蛋白，以形成细胞内的第二信使，这 依次调制膜的电导和产生的电性 回应。中断任何将气味物质结合到 电反应的产生将导致功能损害。 气味受体的几个家族以及气味受体的许多成分 利用分子克隆技术已经鉴定出了转导级联。 然而，受体的功能性表达和与特定受体的匹配 其同源气味在哺乳动物身上被证明是一项艰巨的任务，在那里 可能有上千个感受器和成千上万的气味。鱼的反应 气味少得多，气味感受器也少了一个数量级。 我们将使用分子和电生理方法来表征 原始脊椎动物模型中的嗅觉传导。海洋七鳗鱼似乎 只对几十种气味有反应。假设相应地受限于 气味感受器的数量，气味与其 受体大大增加。几种氨基酸气味，还有两种 信息素，已经在这个系统中被识别出来，以及几个编码的cDNA 推测的气味受体已经被分离出来。一旦全长克隆成为 一旦获得，它们将以在异源系统中表达为特征。这个 结果将有助于阐明至少一个完整的信号转导 脊椎动物感受器神经元中的级联反应，源于气味与 产生动作电位的受体。

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.