MOLECULAR MECHANISMS OF VOMERONASAL SENSORY TRANSDUCTION

犁鼻感觉传导的分子机制

• 批准号: 6189010
• 负责人: EMILY R. LIMAN
• 金额: $ 23.36万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6189010
• 关键词: Drosophilidae; biological signal transduction; complementary DNA; genetic library; isomerase; laboratory rat; membrane channels; membrane proteins; second messengers; visual phototransduction; voltage /patch clamp; vomeronasal systems; yeast two hybrid system

DESCRIPTION: (adapted from applicant's abstract)The mammalian olfactory system consists of at least two functionally distinct organs, the main olfactory epithelium and the vomeronasal organ (VNO). The VNO, a pair of tubular structures at the rostral end of the nasal cavity, is thought to mediate detection of pheromones, chemical signals that regulate reproductive and social behavior and neuroendocrine status. Sensory transduction in the VNO is distinct from that in the main olfactory epithelium, and remains poorly understood. The experiments proposed in this application will test the hypothesis that sensory transduction in the VNO is mediated by a signaling pathway similar to that which mediates phototransduction in invertebrates. In support of this hypothesis, the PI has recently found a VNO-specific homolog (TRP2) of the Drosophila light-activated channel (dTRP) that is highly localized to sensory microvilli of rat vomeronasal sensory neurons. The proposed research is aimed at elucidating the role of the TRP2 channel in vomeronasal sensory transduction, and in VNO-mediated behaviors. A central goal of this work is to identify second messenger pathways that activate TRP2. Extensive studies in Drosophila suggest that activation of dTRP is downstream of phospholipase C, but the direct stimulus for opening dTRP channels is not known. The PI will use techniques of patch-clamp recording and ratiometric calcium imaging in heterologous cell types to study gating of TRP2 in response to receptor-mediated stimulation of phospholipase C and direct application of putative second messengers. A second goal is to identify molecules that interact with TRP2 in a yeast two-hybrid screen of a VNO-cDNA library. By analogy to Drosophila phototransduction, the PI expects TRP2 to be part of a signaling complex that includes other components of the sensory transduction cascade. It has recently been recognized that air-borne pheromones play a role in regulating human reproduction as seen in the menstrual synchrony of women who are in close contact. The sensory reception of human pheromones is not well understood, but may be mediated by the VNO, a structure previously thought to be vestigial in humans. The proposed experiments to elucidate basic mechanisms of sensory transduction in the VNO may, thus, provide a better understanding of the control of human reproductive function.

描述：（改编自申请人摘要）哺乳动物嗅觉系统 由至少两个功能不同的器官组成，主要的嗅觉器官 上皮和犁鼻器（VNO）。VNO，一对管状 鼻腔的喙端结构，被认为是介导 检测信息素，调节生殖和社会的化学信号 行为和神经内分泌状态。VNO的感觉传导是不同的 与主要的嗅上皮细胞不同，并且仍然知之甚少。的 本申请中提出的实验将测试感官的假设 VNO中的转导是由类似于 在无脊椎动物中介导光传导。为支持这一 假设，PI最近发现了VNO特异性同源物（TRP 2）， 果蝇光激活通道（dTRP），高度定位于感觉神经元， 大鼠犁鼻感觉神经元的微绒毛。拟议的研究旨在 在阐明TRP 2通道在犁鼻感觉中的作用方面， 转导和VNO介导的行为。这项工作的中心目标是 识别激活TRP 2的第二信使途径。广泛研究 果蝇表明dTRP的激活在磷脂酶C的下游， 但开放dTRP通道的直接刺激尚不清楚。PI将使用 膜片钳记录和比率钙显像技术， 异源细胞类型，以研究TRP 2响应于 受体介导的磷脂酶C刺激和直接应用 假定的第二信使。第二个目标是鉴定出 在酵母双杂交筛选VNO-cDNA文库中与TRP 2相互作用。 通过类比果蝇光转导，PI预期TRP 2是一个蛋白质的一部分。 包括感觉传导的其它成分的信号复合物 级联。最近人们认识到，空气传播的信息素发挥作用， 在调节人类生殖方面， 密切接触的人。人类信息素的感官接收并不好 可以理解，但可能是由VNO介导的，VNO是一种以前认为 在人类中是退化的。为阐明基本机制而提出的实验 因此，VNO中的感觉转导可以提供更好的理解， 控制人类的生殖功能。