MOLECULAR MECHANISMS OF VOMERONASAL SENSORY TRANSDUCTION

描述：(改编自申请者摘要)哺乳动物的嗅觉系统 由至少两个功能不同的器官组成，主要嗅觉 上皮和犁鼻器(VNO)。VNO，一对管状 位于鼻腔吻端的结构，被认为起调节作用 信息素的检测，这是调节生殖和社会的化学信号 行为和神经内分泌状态。VNO中的感觉传导是明显的 从主要的嗅觉上皮细胞中分离出来，至今仍知之甚少。这个 本申请中提出的实验将检验感官的假设 VNO中的信号转导是由一个类似于 参与无脊椎动物的光转导。为了支持这一点 假设，PI最近发现了一个VNO特异的同源基因(Trp2) 高度定位于感觉的果蝇光激活通道(DTRP) 大鼠犁鼻感觉神经元的微绒毛。拟议中的研究旨在 在阐明Trp2通道在犁鼻感觉中的作用 转导，以及VNO介导的行为。这项工作的一个中心目标是 确定激活Trp2的第二个信使通路。对……的广泛研究 果蝇认为dTrp的激活位于磷脂酶C的下游， 但开放dTrp通道的直接刺激因素尚不清楚。PI将使用 膜片钳记录技术和比率钙成像技术的研究 异源细胞类型研究Trp2的门控反应 受体介导的磷脂酶C刺激及其直接应用 可能是第二个信使。第二个目标是识别 在酵母双杂交筛选的VNO-cDNA文库中与Trp2相互作用。 通过与果蝇光转导的类比，PI预计Trp2是 包括感觉转导的其他组成部分的信号复合体 卡斯卡德。最近人们认识到，空气中的信息素在 在调节人类生殖方面，如女性月经同步性所见 有密切联系的人。人类信息素的感官接受能力不强。 可以理解，但可能是由VNO介导的，这一结构以前被认为是 对人类来说是退化的。为阐明基本机制而提议的实验 因此，对VNO中感觉转导的研究可能会提供更好的理解 对人类生殖功能的控制。

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.