Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells
Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells
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DOI：
10.1523/jneurosci.1168-07.2007
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发表时间：
2007-11-14
影响因子：
5.3
通讯作者：
Meyerhof, Wolfgang
中科院分区：
文献类型：
--
作者：
Behrens, Maik;Foerster, Susann;Meyerhof, Wolfgang
人类的苦味是由类似于人类TAS 2受体（hTAS 2 R）基因家族的25个成员介导的。hTAS 2 R基因在舌面味觉乳头的味蕾中表达。由于许多天然存在的苦味化合物是有毒的，苦味受体被认为是针对摄入有毒食物化合物的警告传感器。一个重要的问题是，苦味受体细胞是否是一个均匀的，广泛调谐的细胞群，均匀表达所有的苦味受体基因，或者不是。啮齿类动物的基因表达分析表明，TAS 2 R基因的表达基本上是重叠的，表明一个广泛的调整，而在体内的功能分析表明，一个狭窄的调整。本研究证明了所有25个人TAS 2 R基因在人轮廓乳头味觉感受器细胞中的表达。如原位杂交实验所示，hTAS 2 R基因的表达在表观表达水平和表达这些基因的味觉受体细胞的数量上都不同，这表明苦味受体细胞群是异质的。基因表达水平的差异通过hTAS 2 R基因子集的定量逆转录-PCR实验进行验证。苦味受体细胞异质性的直接证据是通过与选定的hTAS 2 R基因特异性探针对的双标记原位杂交提供的。异源细胞中的功能性共表达实验显示hTAS 2 R之间的竞争，表明所观察到的表达模式的可能的生物学原因。从这些数据中，我们得出结论，人类苦味受体细胞被调谐以检测苦味刺激的有限子集。
Human bitter taste is mediated by similar to 25 members of the human TAS2 receptor (hTAS2R) gene family. The hTAS2R genes are expressed in taste buds of gustatory papillae on the tongue surface. Because many naturally occurring bitter compounds are toxic, bitter taste receptors are believed to serve as warning sensors against the ingestion of toxic food compounds. An important question is whether bitter taste receptor cells are a homogeneous, broadly tuned population of cells, which uniformly express all bitter taste receptor genes, or not. Gene expression analyses in rodents demonstrated an essentially overlapping expression of TAS2R genes indicating a broad tuning, whereas functional in vivo analyses suggest a narrow tuning. The present study demonstrates the expression of all 25 human TAS2R genes in taste receptor cells of human circumvallate papillae. As shown by in situ hybridization experiments, the expression of hTAS2R genes differs in both the apparent level of expression and the number of taste receptor cells expressing these genes, suggesting a heterogeneous bitter taste receptor cell population. Differences in gene expression levels were verified by quantitative reverse transcription-PCR experiments for a subset of hTAS2R genes. Direct evidence for the heterogeneity of bitter taste receptor cells is provided by dual-labeling in situ hybridizations with selected pairs of hTAS2R gene-specific probes. Functional coexpression experiments in heterologous cells show competition among hTAS2Rs, indicating a possible biological reason for the observed expression pattern. From the data, we conclude that human bitter taste receptor cells are tuned to detect a limited subset of bitter stimuli.