Functional Interaction between T2R Taste Receptors and G-Protein α Subunits Expressed in Taste Receptor Cells
Functional Interaction between T2R Taste Receptors and G-Protein α Subunits Expressed in Taste Receptor Cells
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DOI：
10.1523/jneurosci.23-19-07376.2003
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发表时间：
2003-08
期刊：
影响因子：
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通讯作者：
T. Ueda;S. Ugawa;H. Yamamura;Y. Imaizumi;S. Shimada
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文献类型：
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作者：
T. Ueda;S. Ugawa;H. Yamamura;Y. Imaizumi;S. Shimada
苦味知觉是哺乳动物对有毒物质摄取的一种保守的化学感觉。G蛋白偶联受体的多基因家族T2R(所谓的TAS2R或TrB)受体和G蛋白α亚单位(Gα)Gustducin被认为是其感知的关键分子，但对其相互作用的分子基础知之甚少。在这里，我们使用异源表达系统来确定T2R偶联所需的Gustducin的特定结构域。两个在C端含有37和44个Gustducin特异序列的嵌合Gα16蛋白(G16/Gust37和G16/Gust44)与不同的T2R受体反应，但G16/Gust23、G16/Gust11和G16/Gust5不能与不同的T2R受体反应。前两个嵌合体包含一个预测的β6片断、一个α5螺旋和一个极端的Gustducin C末端，所有这些结构域都是表达T2R活性所必需的。我们还表达了与其他GαI蛋白、锥体转导蛋白(GαT2)、Gαi2和Gαz(G16/T2、G16/i2和G16/z)对应的结构域的G16蛋白嵌合体。因此，G16/T2和G16/i2产生了T2Rs的特异性反应，而G16/z没有。由于G-αT2和G-αi2在味觉感受器细胞中表达，这些G-蛋白αI亚基也可能通过T2R受体参与苦味感受。目前基于Gα16的嵌合体可能是分析许多孤儿G蛋白偶联味觉受体功能的有用工具。
Bitter taste perception is a conserved chemical sense against the ingestion of poisonous substances in mammals. A multigene family of G-protein-coupled receptors, T2R (so-called TAS2R or TRB) receptors and a G-protein α subunit (Gα), gustducin, are believed to be key molecules for its perception, but little is known about the molecular basis for its interaction. Here, we use a heterologous expression system to determine a specific domain of gustducin necessary for T2R coupling. Two chimeric Gα16 proteins harboring 37 and 44 gustducin-specific sequences at their C termini (G16/gust37 and G16/gust44) responded to different T2R receptors with known ligands, but G16/gust 23, G16/gust11, and G16/gust5 did not. The former two chimeras contained a predictedβ6 sheet, anα5 helix, and an extreme C terminus of gustducin, and all the domains were indispensable to the expression of T2R activity. We also expressed G16 protein chimeras with the corresponding domain from other Gαi proteins, cone-transducin (Gαt2), Gαi2, and Gαz (G16/t2, G16/i2, and G16/z). As a result, G16/t2 and G16/i2 produced specific responses of T2Rs, but G16/z did not. Because Gαt2 and Gαi2 are expressed in the taste receptor cells, these G-protein αi subunits may also be involved in bitter taste perception via T2R receptors. The present Gα16-based chimeras could be useful tools to analyze the functions of many orphan G-protein-coupled taste receptors.