Mechanisms of Olfactory Transduction

嗅觉在我们的一般生活质量和福祉中发挥着越来越重要的作用， 这一角色因疾病、药物、老龄化和环境冲击对我们的影响而受到损害 化学感官能力。鼻子中的感受器神经元起着检测和识别 传递气味的物质。任何导致受体细胞激活的细胞内事件的破坏都可以 会导致嗅觉功能障碍。新的证据表明，磷脂酰肌醇信号转导和短暂性 化学感觉中该信号通路共同靶向的受体电位(Trp)离子通道 味觉感受器细胞、犁鼻感受器神经元、无脊椎动物嗅觉感受器神经元、 可能还存在于脊椎动物的嗅觉感受器神经元中，最近的证据表明，它可以调节 成熟的环核苷酸信号通路。肌醇磷脂信号转导本来就很复杂，而且 这种复杂性阻碍了人们对其在许多蜂窝系统中的作用的清楚了解。在这个持续的过程中 项目中，我们使用集成的分子、生化和电生理方法来进一步定义 嗅觉系统中肌醇磷脂信号的细胞机制。我们使用了一个动物模型 其中，肌醇磷脂信号在嗅觉转导中的功能作用尤为突出 已经确定，并导致证据表明，磷脂酰肌醇信号转导在 脊椎动物的嗅觉。这个项目有可能识别新的细胞和分子事件 参与嗅觉感受器细胞的激活，并有助于更全面地了解 磷脂信号和色氨酸通道在化学传感中的作用。

The sense of smell plays an increasingly appreciated role in our general quality of life and well being, a role that is compromised by the effect of disease, drugs, aging and environmental onslaught on our chemosensory competence. Receptor neurons in the nose serve the critical function of detecting and transducing odorants. Disruption of any of the intracellular events leading to receptor cell activation can result in olfactory dysfunction. Emerging evidence implicates phosphoinositide signaling and the transient receptor potential (TRP) ion channels commonly targeted by this signaling pathway in chemosensory transduction in taste receptor cells, vomeronasal receptor neurons, invertebrate olfactory receptor neurons, and possibly in vertebrate olfactory receptor neurons, where recent evidence suggests it can modulate the well established cyclic nucleotide signaling pathway. Phosphoinositide signaling is inherently complex, and this complexity has impeded a clear understanding of its role in many cellular systems. In this continuing project, we use an integrated, molecular, biochemical, and electrophysiologicalapproach to further define the cellular mechanisms of phosphoinositide signaling in an olfactory system. We use an animal model in which the functional role of phosphoinositide signaling in olfactory transduction is particularly well established, and has led to the evidence suggesting a potential role for phosphoinositide signaling in vertebrate olfaction. This project has the potential to identify new cellular and molecular events potentially involved in olfactory receptor cell activation, as well as contribute to a more general understanding of phospholipid signaling and TRP channel function in chemical sensing.