Mechanisms of Olfactory Transduction

嗅觉传导机制

• 批准号: 7850378
• 负责人: Barry W. ACHE
• 金额: $ 37.29万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850378
• 关键词: Aging; Animal Model; Biochemical; Cations; Chemicals; Cloning; Competence; Complex; Cyclic Nucleotides; Disease; Event; Functional disorder; GTP-Binding Proteins; Inositol Phosphates; Invertebrates; Ion Channel; Lobster; Mediating; Molecular; Neurons; Nose; Odors; Olfactory Receptor Cells; Olfactory Receptor Neurons; Output; Pharmaceutical Preparations; Phosphatidylinositols; Phospholipids; Phosphorylation; Play; Quality of life; Receptor Cell; Regulation; Relative (related person); Role; Signal Pathway; Signal Transduction; Smell Perception; System; Taste Perception; in vivo; receptor

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.

嗅觉在我们的总体生活质量和健康方面发挥着越来越重要的作用， 这一角色受到疾病、药物、衰老和环境对我们的冲击的影响， 化学感受能力鼻子中的受体神经元起着检测和 传递气味。导致受体细胞活化的任何细胞内事件的破坏可以 导致嗅觉功能障碍。新出现的证据表明磷酸肌醇信号和瞬时 受体电位（TRP）离子通道通常在化学感受器中被该信号通路靶向。 味觉受体细胞、犁鼻受体神经元、无脊椎动物嗅觉受体神经元， 可能在脊椎动物的嗅觉受体神经元中，最近的证据表明它可以调节 已建立的环核苷酸信号传导途径。磷脂酰肌醇信号转导是固有的复杂， 这种复杂性阻碍了对其在许多蜂窝系统中的作用的清楚理解。在这场持续的 项目，我们使用综合的，分子，生物化学和电生理学的方法，以进一步定义 嗅觉系统中磷酸肌醇信号传导的细胞机制。我们使用动物模型， 其中磷酸肌醇信号在嗅觉传导中的功能作用特别好， 已经建立，并导致证据表明磷酸肌醇信号转导的潜在作用， 脊椎动物的嗅觉该项目有可能识别新的细胞和分子事件， 参与嗅觉受体细胞激活，以及有助于更全面地了解 磷脂信号传导和TRP通道在化学传感中的功能。