T2Rs function as bitter taste receptors
T2Rs function as bitter taste receptors
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DOI：
10.1016/s0092-8674(00)80706-0
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发表时间：
2000-03-17
期刊：
影响因子：
64.5
通讯作者：
Ryba, NJP
中科院分区：
文献类型：
--
作者：
Chandrashekar, J;Mueller, KL;Ryba, NJP
苦味感知为动物提供了重要的保护，以防止摄入有毒化合物。在随附的文件中，我们报告了一个大家庭的推定哺乳动物味觉受体（T2 Rs）的表征。在这里，我们使用一个异源表达系统，以显示特定的T2受体作为苦味受体的功能。小鼠T2 R（mT 2 R-5）对苦味剂放线菌酮有反应，人和小鼠的受体（hT 2 R-4和mT 2 R-8）对地那铵和6-正丙基-2-硫氧嘧啶有反应。检测放线菌酮能力不足的小鼠品系在mT 2 R-5基因中具有氨基酸取代;这些变化使受体对放线菌酮的反应显着降低。我们还在昆虫细胞中表达了mT 2 R-5，并证明了味觉蛋白（一种与苦味信号有关的G蛋白）的特异性味觉依赖性激活。由于单个味觉受体细胞表达大量T2 R，这些发现为许多结构无关的有毒化合物引起的均匀苦味提供了合理的解释。
Bitter taste perception provides animals with critical protection against ingestion of poisonous compounds. In the accompanying paper, we report the characterization of a large family of putative mammalian taste receptors (T2Rs). Here we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains deficient in their ability to detect cycloheximide have amino acid substitutions in the mT2R-5 gene; these changes render the receptor significantly less responsive to cycloheximide. We also expressed mT2R-5 in insect cells and demonstrate specific tastant-dependent activation of gustducin, a G protein implicated in bitter signaling. Since a single taste receptor cell expresses a large repertoire of T2Rs, these findings provide a plausible explanation for the uniform bitter taste that is evoked by many structurally unrelated toxic compounds.