Species differences and molecular determinant of TRPA1 cold sensitivity.
Species differences and molecular determinant of TRPA1 cold sensitivity.
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DOI：
10.1038/ncomms3501
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发表时间：
2013
影响因子：
16.6
通讯作者：
Kim, Donghee
中科院分区：
文献类型：
--
作者：
Chen, Jun;Kang, Dawon;Xu, Jing;Lake, Marc;Hogan, James O.;Sun, Chaohong;Walter, Karl;Yao, Betty;Kim, Donghee
TRPA 1是一种离子通道，已被提议作为跨物种的温度传感器。在无脊椎动物和祖先脊椎动物如苍蝇、蚊子、青蛙、蜥蜴和蛇中，TRPA 1作为热受体，用于热回避或红外检测的感觉输入。然而，在哺乳动物中，TRPA 1是否是有害寒冷的受体是非常有争议的，因为一些小组观察到寒冷激活通道，但另一些人则有争议。在这里，我们把这种差异归因于物种差异。我们发现，寒冷激活大鼠和小鼠TRPA 1，但不激活人类或恒河猴TRPA 1。在分子水平上，S5跨膜结构域内的单个残基（啮齿动物中的G878，而灵长类动物中的V875）解释了所观察到的冷敏感性差异。这种残留差异也是薄荷醇的物种特异性效应的基础。总之，我们的研究结果确定了TRPA 1的物种特异性冷激活，并揭示了冷敏感门控的分子决定因素。 TRPA 1离子通道作为温度传感器在不同的物种;然而，对它们在有害的冷感觉中的作用的研究在哺乳动物中提供了相互矛盾的结果。Chen等人表明，这些差异的出现是因为寒冷激活了大鼠和小鼠的TRPA 1，而不是人类或恒河猴的TRPA 1。
TRPA1 is an ion channel and has been proposed as a thermosensor across species. In invertebrate and ancestral vertebrates such as fly, mosquito, frog, lizard and snakes, TRPA1 serves as a heat receptor, a sensory input utilized for heat avoidance or infrared detection. However, in mammals, whether TRPA1 is a receptor for noxious cold is highly controversial, as channel activation by cold was observed by some groups but disputed by others. Here we attribute the discrepancy to species differences. We show that cold activates rat and mouse TRPA1 but not human or rhesus monkey TRPA1. At the molecular level, a single residue within the S5 transmembrane domain (G878 in rodent but V875 in primate) accounts for the observed difference in cold sensitivity. This residue difference also underlies the species-specific effects of menthol. Together, our findings identify the species-specific cold activation of TRPA1 and reveal a molecular determinant of cold-sensitive gating. TRPA1 ion channels act as thermosensors across different species; however, studies on their role in noxious cold sensation have provided conflicting results in mammals. Chen et al. show that these discrepancies arise because cold activates rat and mouse TRPA1 but not human or rhesus monkey TRPA1.
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影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1523/jneurosci.5369-07.2008
发表时间：
2008-03-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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作者：
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DOI：
10.1124/jpet.111.189902
发表时间：
2012-05-01
影响因子：
3.5
作者：
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通讯作者：
Chen, Jun
影响因子：
16.2
作者：
Kwan, KY;Allchorne, AJ;Corey, DP
通讯作者：
Corey, DP