Molecular bases of odor discrimination: Reconstitution of olfactory receptors that recognize overlapping sets of odorants
Molecular bases of odor discrimination: Reconstitution of olfactory receptors that recognize overlapping sets of odorants
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DOI：
10.1523/jneurosci.21-16-06018.2001
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发表时间：
2001-08-15
影响因子：
5.3
通讯作者：
Touhara, K
中科院分区：
文献类型：
--
作者：
Kajiya, K;Inaki, K;Touhara, K
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1000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+成像和单细胞逆转录-PCR技术，以确定小鼠嗅觉神经元响应的气味剂，随后克隆受体基因的响应细胞。功能克隆的受体在异源系统中表达，表明结构上相关的嗅觉受体识别重叠的气味具有不同的亲和力和特异性。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，我们表明，气味受体在人胚肾293细胞耦合到刺激G-蛋白，如G α olf，导致气味依赖性增加cAMP。因此，气味辨别是由共同编码特定气味分子的气味受体的接受范围的差异决定的。
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 similar to 1000 distinct olfactory receptors, which comprise the largest family of G-protein-coupled receptors. In the present study, we used Ca2+ imaging and single-cell reverse transcription-PCR techniques to identify mouse olfactory neurons responding to an odorant and subsequently to clone a receptor gene from the responsive cell. The functionally cloned receptors were expressed in heterologous systems, demonstrating that structurally related olfactory receptors recognized 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 human embryonic kidney 293 cells couple to stimulatory G-proteins such as G alpha olf, 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.