Olfactory receptors for semiochemical detection in the main olfactory epithelium

 描述(申请人提供)：我们实验室最近的工作表明，在小鼠中，表达瞬时受体电位通道M5(Trpm5)的嗅觉感觉神经元(OSN)的子集对信号化学物质(参与动物交流的化学物质，源自希腊语中“符号”的意思)做出反应，包括推定的信息素、主要组织相容性复合体(MHC)的多肽和尿液(2)。因此，对信息素和其他信号化学物质的反应并不完全是由犁鼻器介导的。在这项研究中，我们将测试这样一种假设，即表达Trpm5的OSN子集使用特定的嗅觉受体子集对信号化学物质做出反应。重要的是，尽管人类似乎不表达犁鼻器，但数据表明，他们对推测的信息素和其他信号化学物质有反应(4，5)。因此，我们将在老鼠和人类身上进行实验，寻找对信号化学物质的反应。我们利用强大的技术，包括记录单个OSN，用RNA-Seq评估这些神经元中嗅觉受体的表达，以及记录特定嗅觉受体对大量信号化学物质和气味的反应，提出了三个特定的目标：目的1.验证小鼠Trpm5+OSNs中嗅觉受体在两性中差异表达的假设。目的2.Trpm5+OSNs是否参与人类和小鼠对低浓度信号化学物质的反应？目的3.验证Trpm5表达的OSN表达的嗅觉受体对低浓度的信号化学物质有反应的假说。 相关性：这笔赠款将检查小鼠和人类主要嗅觉上皮的嗅觉感觉神经元，以识别对信号化学物质做出反应的嗅觉感受器，包括推测的信息素、主要组织相容性复合肽和从体内释放的液体。这项研究对于理解人类的化学感受特别相关，因为人类没有功能性的犁鼻器，可能利用主要的嗅觉系统来检测信号化学物质(5，8)。识别可以操纵人类荷尔蒙系统的挥发性分子将是控制人类健康的重要的非侵入性方法。我们的研究将为主要嗅觉系统中介导信号化学感觉的嗅觉受体提供新的信息。

 DESCRIPTION (provided by applicant): Recent work from our laboratory shows that in mice a subset of the olfactory sensory neurons (OSNs) that express the transient receptor potential channel M5 (TRPM5) respond to semiochemicals (chemicals involved in animal communication, from the Greek semeion for ``sign'') including putative pheromones, peptides from the major histocompatibility complex (MHC) and urine (2). Therefore, the response to putative pheromones and other semiochemicals is not mediated exclusively by the vomeronasal organ. In this grant we will test the hypothesis that this subset of OSNs expressing TRPM5 respond to semiochemicals using a specific subset of olfactory receptors. Importantly, despite the fact that humans do not appear to express a vomeronasal organ, data suggest that they respond to putative pheromones and other semiochemicals (4, 5). Therefore we will perform experiments searching for responses to semiochemicals in mice and humans. Using strong techniques involving recording from single OSNs, evaluation of olfactory receptor expression in these neurons using RNA-Seq, and recording responses of specific olfactory receptors to large numbers of semiochemicals and odorants we propose three specific aims: Aim 1. Test the hypothesis that olfactory receptors in mouse TRPM5+ OSNs are differentially expressed in the two genders. Aim 2. Are TRPM5+ OSNs involved in responses to semiochemicals at low concentrations in both human and mouse? Aim 3. Test the hypothesis that olfactory receptors expressed in TRPM5-expressing OSNs respond to semiochemicals at low concentrations. RELEVANCE: This grant will examine olfactory sensory neurons from the main olfactory epithelium of mice and humans to identify olfactory receptors that respond to semiochemicals including putative pheromones, major histocompatibility complex peptides and liquids released from the body. This study is particularly relevant to understand human chemoreception, as humans do not have a functional vomeronasal organ and may utilize the main olfactory system for detection of semiochemicals (5, 8). Identifying volatile molecules that can manipulate the hormonal system of humans would be an important non-invasive method for control of human health. Our studies will provide novel information on olfactory receptors mediating semiochemical sensing in the main olfactory system.