Reconstitution and visualization of odorant responses in olfactory neurons

嗅觉神经元气味反应的重建和可视化

• 批准号: 11680661
• 负责人: TOUHARA Kazushige
• 金额: $ 2.37万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680661/
• 关键词: odorant; receptor; olfactory; 可視化

The vertebrate olfactory system discriminates a wide variety of odorants by relaying coded information from olfactory sensory neurons in the olfactory epithelium to olfactory cortical areas of the brain. Recent studies have shown that the first step in odor discrimination is mediated by approximately one thousand distinct olfactory receptors, which comprise the largest family of G protein-coupled receptors. In the present study, we used Ca^<2+> imaging techniques to functionally clone and reconstitute structurally-related mouse olfactory receptors that bind overlapping sets of odorants with distinct affinities and specificities. Our results provide direct evidence for the existence of a receptor code in which the identities of different odorants are specified by distinct combinations of odorant receptors that possess unique molecular receptive ranges. We further demonstrate that the receptor code for an odorant changes with odorant concentration. Finally, we show that odorant receptors in HEK293T cells couple to stimulatory G proteins such as Gαolf, resulting in odorant-dependent increases in cAMP.Odor discrimination is thus determined by differences in the receptive ranges of the odorant receptors that together encode specific odorant molecules.

脊椎动物的嗅觉系统通过将编码信息从嗅觉上皮中的嗅觉感觉神经元传递到大脑的嗅觉皮层区域来辨别各种各样的气味。最近的研究表明，气味辨别的第一步是由大约一千种不同的嗅觉受体介导的，这些受体包括最大的G蛋白偶联受体家族。在本研究中，我们使用Ca^2+成像技术功能性克隆和重建结构相关的小鼠嗅觉受体，这些受体以不同的亲和力和特异性结合重叠的气味物。我们的研究结果提供了直接的证据，受体代码的存在，其中的身份不同的气味指定的气味受体，具有独特的分子接受范围的不同组合。我们进一步证明，受体代码的气味的变化与气味的浓度。最后，我们发现HEK293T细胞中的气味受体与刺激性G蛋白（如Gαolf）偶联，导致cAMP的气味依赖性增加。因此，气味辨别是由共同编码特定气味分子的气味受体的感受范围差异决定的。

项目成果

Touhara, K.: "Molecular mechanisms of odor recognition : biochemistry and molecular biology of olfactory receptors"Cell Technology. 19. 111-119 (2000)

Touhara, K.：“气味识别的分子机制：嗅觉受体的生物化学和分子生物学”细胞技术。

東原和成: "Functional cloning and reconstitution of vertebrate odorant receptors"Life Sciences. (発表予定).

Kazunari Higashihara：“脊椎动物气味受体的功能克隆和重建”生命科学（待提交）。

東原和成: "Molecular bases of odor discrimination by G protein-coupled olfactory receptors"Microscopic Research and Technology. (発表予定).

Kazunari Higashihara：“G 蛋白偶联嗅觉受体辨别气味的分子基础”微观研究和技术（待提交）。

東原和成: "嗅覚受容体は匂いを嗅いでいるのか?"医学のあゆみ. 194. 152-153 (2000)

Kazunari Higashihara：“嗅觉感受器有气味吗？” 194. 152-153 (2000)

Touhara, K.: "Do odorant receptors smell?"J.Clin.Exp.Med.. 194. 152-153 (2000)

Touhara, K.：“气味受体有气味吗？”J.Clin.Exp.Med.. 194. 152-153 (2000)