MECHANOTRANSDUCTION IN C ELEGANS

秀丽隐杆线虫的机械传导

• 批准号: 2270205
• 负责人: JOSHUA M KAPLAN
• 金额: $ 24.23万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2270205
• 关键词: MECHANOTRANSDUCTION; ELEGANS

How is a mechanical stimulus, such as touch or sound, transduced by the nervous system into a physiological response? Despite the substantial progress made in characterizing the receptors underlying vision, smell, and taste, very little is known about the molecular basis of mechanotransduction. We propose to identify and characterize the molecules required for mechanotransduction in C. elegans. These molecules may prove to be useful reagents for studying mammalian behavior, for identifying candidate genes for hereditary hearing loss, and for identifying potential targets for novel pharmaceuticals in the clinical management of pain. We have identified a bifunctional C. elegans sensory neuron that responds to both a mechanical stimulus (touch) and to particular chemical repellants. We have devised assays to test the behavioral response to both of these stimuli, and we have used these assays to identify four not genes (nose touch insensitive) that are required specifically for touch sensitivity but not for chemical avoidance. Thus, these four genes may encode molecules that are directly involved in mechanotransduction. First, we will isolate new mutations in these four not genes. These new mutations will allow us to determine if these genes are required in only mechanosensory neurons, or if they are also required in other tissues. These new mutations will also facilitate the molecular cloning of these genes. Second, we will identify new not genes, and determine whether any of these new genes are specifically required for mechanotransduction. Third, we will clone those genes that seem likely to encode molecules that are directly involved in mechanotransduction. Fourth, we will determine which cells express these genes, and the subcellular distribution of each gene product. Fifth, we will attempt to demonstrate that these genes encode functional mechanoreceptors by conferring mechanosensory function on novel cells by ectopic expression of these not genes. In summary, these experiments should allow us to identify a set of genes that encode molecules that are directly involved in mechanotransduction, or which regulate the function or expression of the mechanotransduction apparatus. The identification of these molecules will provide us with the tools necessary to answer one of the enduring mysteries of neurobiology -- what are the molecular mechanisms underlying mechanosensation and modality coding of mechanical stimuli.

机械刺激是如何通过触摸或声音的 神经系统对生理反应？ 尽管有实质性 在表征视觉，气味的受体表征方面取得的进展 和味道，关于分子基础知之甚少 机械转导。 我们建议识别和表征 秀丽隐杆线虫中机械转导所需的分子。 这些 分子可能被证明是研究哺乳动物的有用试剂 行为，用于识别遗传性听力损失的候选基因， 并确定新型药物的潜在靶标 疼痛的临床管理。 我们已经确定了一个反应的双功能秀丽隐杆线虫感官神经元 要进行机械刺激（触摸）和特定化学物质 驱虫剂。 我们已经设计了测定法以测试行为响应 这两种刺激都 专门为触摸所需的基因（鼻子触摸不敏感） 敏感性，但不是为了避免化学物质。 因此，这四个基因可能 编码直接参与机械转导的分子。 首先，我们将在这四个非基因中隔离新突变。 这些新 突变将使我们能够确定是否仅在 机械感觉神经元，或者在其他组织中也需要它们。 这些新突变也将促进这些突变的分子克隆 基因。 第二，我们将确定新基因，并确定是否有 这些新基因是机械转移所需的。 第三，我们将克隆那些似乎可以编码分子的基因 直接参与机械转导的。 第四，我们会的 确定哪些细胞表达这些基因，以及亚细胞 每个基因产物的分布。 第五，我们将尝试证明 这些基因通过赋予功能机械感受器编码 通过异位表达这些非 基因。 总而言之，这些实验应使我们能够识别一组基因 该编码直接参与机械转导的分子， 或调节机械转移的功能或表达 设备。 这些分子的识别将为我们提供 回答一个持久的奥秘所需的工具 神经生物学 - 依据的分子机制是什么 机械刺激的机械密度和模态编码。