Phosphoinositide signaling in mammalian olfaction

哺乳动物嗅觉中的磷酸肌醇信号传导

• 批准号: 8579794
• 负责人: Barry W. ACHE
• 金额: $ 31.13万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8579794
• 关键词: Address; Age; Aging; Biochemical; Brain; Cell physiology; Cells; Cilia; Code; Complex; Cyclic AMP; Cyclic Nucleotides; Data; Dementia; Disease; Enzymes; Event; Functional disorder; Image; Individual; Mediating; Molecular; Nature; Odors; Olfactory Epithelium; Olfactory Receptor Cells; Olfactory Receptor Neurons; Output; PIK3CG gene; Pathway interactions; Pharmaceutical Preparations; Phosphatidylinositols; Play; Population; Protein Isoforms; Quality of life; Relative (related person); Rodent; Role; Series; Signal Pathway; Signal Transduction; Smell Perception; Specificity; System; Targeted Research; Testing; Viral; Work; follow-up; in vivo; insight; public health relevance; research study

DESCRIPTION (provided by applicant): Odors play 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 the olfactory epithelium. As olfactory receptor neurons (ORNs) in the olfactory epithelium provide the primary input to the olfactory system, disruption of any of the cellular processes leading to the activation of the ORNs inevitably compromises impairs olfactory function. This project builds on our emerging understanding that the organization of the olfactory periphery is more complex than originally appreciated. It specifically addresses a largely ignored aspect of that complexity, which is how odorants are able to inhibit as well as excite ORNs. It tests the hypothesis, built on increasingly compelling data, that phosphoinositide (PI) signaling mediates inhibitory input to mammalian ORNs and plays an important role in setting the output of the ORNs evoked by natural, complex odorants. A series of focused, electrophysiological, biochemical, and molecular experiments address this question by continuing to evaluate the functional significance of PI signaling in rodent ORNs, and beginning to identify the cellular mechanisms through which PI signaling works. The idea that inhibitory input is mediated through a distinct input pathway from that mediating excitation represents important new insight into the sense of smell, insight that not only raises fundamental questions about the nature of the OR itself but also about the importance of inhibitory input to olfactory coding in having a separate signaling pathway assigned to it.

描述(申请人提供)：气味在我们的一般生活质量和福祉中扮演着越来越重要的角色，这个角色因疾病、药物、衰老和环境对嗅觉上皮的冲击而受到影响。由于嗅觉上皮中的嗅觉感受器神经元为嗅觉系统提供主要的输入，任何导致嗅觉感受器神经元激活的细胞过程的中断都不可避免地损害嗅觉功能。这个项目建立在我们正在形成的理解之上，即嗅觉外周的组织比最初意识到的更复杂。它特别提到了复杂性中一个被很大程度上忽视的方面，那就是气味如何能够抑制和刺激兽人。它检验了建立在越来越令人信服的数据基础上的假设，即磷脂酰肌醇(PI)信号介导了哺乳动物Ons的抑制性输入，并在设定天然复杂气味引起的On的输出方面发挥了重要作用。一系列集中的电生理、生化和分子实验通过继续评估PI信号在啮齿类动物Orns中的功能意义，并开始确定PI信号工作的细胞机制来解决这一问题。抑制性输入是通过一条不同于介导兴奋的不同的输入通路传递的，这一观点代表了对嗅觉的重要的新见解，这一见解不仅提出了关于OR本身性质的基本问题，而且还提出了抑制性输入对嗅觉编码的重要性，因为有一个单独的信号通路被分配给它。