GUANYLYL CYCLASE IN OLFACTORY SIGNALING

嗅觉信号中的鸟苷酸环化酶

• 批准号: 6350567
• 负责人: HANS-JURGEN FULLE
• 金额: $ 24.41万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6350567
• 关键词: Adenoviridae; G protein; behavioral /social science research tag; biological signal transduction; calcium binding protein; calcium ion; chemoreceptors; chimeric proteins; complementary DNA; cyclic GMP; enzyme activity; gene mutation; genetically modified animals; guanylate cyclase; immunofluorescence technique; in situ hybridization; laboratory mouse; laboratory rat; neural information processing; olfactions; olfactory nerve; olfactory stimulus; phosphodiesterases; transfection /expression vector; Adenoviridae; G protein; behavioral /social science research tag; biological signal transduction; calcium binding protein; calcium ion; chemoreceptors; chimeric proteins; complementary DNA; cyclic GMP; enzyme activity; gene mutation; genetically modified animals; guanylate cyclase; immunofluorescence technique; in situ hybridization; laboratory mouse; laboratory rat; neural information processing; olfactions; olfactory nerve; olfactory stimulus; phosphodiesterases; transfection /expression vector

The exquisite discriminatory capacity and sensitivity of the mammalian olfactory system is thought to result from a series of complex signal transduction mechanisms that reside within the primary sensory neuron. Odorous molecules are detected by olfactory receptors linked to G-proteins, intracellular second messengers, and ion channels, generating neuronal signals that are conveyed to the brain where this information is processed and perceived as odor. Preliminary studies revealed a subset of olfactory sensory neurons that utilize a cGMP-mediated signaling system and project axons to specific glomeruli in the olfactory bulb, some of which have been implicated as part of a pathway processing odor cues for suckling behavior in neonatal rats. The long-term goal is to understand the diversity of olfactory sensory neurons, identify their signal transduction systems and decipher the neural pathways to, and within, the brain that allow perception of specific odors and control of innate behavior. The hypothesis to be tested contends that a specific subset of olfactory neurons, and the glomeruli to which they project, perform a unique biological function in the mammalian olfactory system. This is mediated by a membrane guanylyl cyclase possibly functioning as an olfactory receptor, coupling cGMP synthesis with changes in neuronal excitability. To test this hypothesis, a multidiscipline approach will characterize the biochemical features of the pathway, including odorant-response characteristics, and the influence of genetic manipulation of pathway components on animal behavior. Double labeling immunofluorescence techniques and single cell reverse transcriptase polymerase chain reactions will allow the identification of molecular components of the signaling systems involved. The biological or chemical signals, eliciting a response in guanylyl cyclase-expressing neurons will be determined, and the contribution of guanylyl cyclase to olfactory signaling and regulation of innate behavior will be evaluated by characterizing the phenotype of mice lacking guanylyl cyclase. This research offers the potential for resolving definitively a role of the cGMP signaling system in olfactory function such as the suckling response of neonates. It is expected to provide further insight into the fundamental mechanisms underlying the transduction, encoding and processing of information in the mammalian chemosensory system. This knowledge will find general application for understanding signaling systems in the brain.

哺乳动物嗅觉系统的精致歧视能力和敏感性被认为是由一系列复杂的信号转导机制所造成的，这些机制位于主要感觉神经元内。 通过与G蛋白，细胞内第二使者和离子通道相关的嗅觉受体检测到了有气味的分子，从而产生神经元信号，这些信号被传递到大脑中，这些信息被处理并被视为气味。 初步研究揭示了嗅觉神经元的一部分，该神经元利用CGMP介导的信号传导系统和项目轴突对嗅球的特定肾小球进行了项目轴突，其中一些涉及途径的一部分是途径处理新生儿大鼠哺乳的通路处理气味的一部分。 长期的目标是了解嗅觉感觉神经元的多样性，确定其信号转导系统，并破译神经途径，并在大脑内部以及内部允许感知特定气味和对先天行为的控制。 要测试的假设认为，嗅觉神经元的特定子集以及它们所预测的肾小球在哺乳动物嗅觉系统中执行独特的生物学功能。 这是由可能充当嗅觉受体起作用的膜鸟鸟环酶介导的，将CGMP合成与神经元兴奋性的变化偶联。 为了检验这一假设，多学科方法将表征该途径的生化特征，包括气味反应特征，以及途径成分基因操纵对动物行为的影响。 双重标记免疫荧光技术和单细胞逆转录酶聚合酶链反应将允许鉴定所涉及的信号系统的分子成分。 将确定表达鸟叶兰群岛环酶神经元中响应的生物或化学信号，并通过表征缺乏鸟叶兰氏环酶的小鼠表征来评估鸟叶烯基环酶对嗅觉信号的贡献以及先天行为的调节。这项研究提供了解决CGMP信号系统在嗅觉功能（例如新生儿的哺乳反应）中的作用的潜力。 预计将进一步了解哺乳动物化学体系系统中信息转导，编码和处理的基本机制。 这些知识将找到理解大脑信号系统的一般应用。