A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene
A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene
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DOI：
10.1016/j.cell.2019.07.034
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发表时间：
2019-09-05
期刊：
影响因子：
64.5
通讯作者：
Xu, X. Z. Shawn
中科院分区：
文献类型：
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作者：
Gong, Jianke;Liu, Jinzhi;Xu, X. Z. Shawn
为了寻找冷敏感受体的分子身份，我们对冷敏感突变体进行了无偏遗传筛选。elegans中，分离出编码红藻氨酸盐型谷氨酸受体的GLR-3基因的突变等位基因。虽然谷氨酸受体是最有名的在中枢神经系统中传递化学突触信号，我们表明，GLR-3的感觉冷在外周感觉神经元ASER触发避冷行为。GLR-3通过G蛋白信号传导冷信号，而不依赖于其谷氨酸门控通道功能，表明GLR-3是一种代谢型冷受体。来自斑马鱼、小鼠和人的脊椎动物GLR-3同源物GluK 2在异源系统中都可以作为冷受体发挥作用。小鼠DRG感觉神经元ex-prc GluK 2，并且这些神经元中的GluK 2敲低抑制它们对冷的敏感性，但不抑制低温。我们的研究确定了一个进化上保守的冷受体，揭示了一个中央化学受体意外地作为一个热受体在外围的功能。
In search of the molecular identities of cold-sensing receptors, we carried out an unbiased genetic screen for cold-sensing mutants in C. elegans and isolated a mutant allele of glr-3 gene that encodes a kainate-type glutamate receptor. While glutamate receptors are best known to transmit chemical synaptic signals in the CNS, we show that GLR-3 senses cold in the peripheral sensory neuron ASER to trigger cold-avoidance behavior. GLR-3 transmits cold signals via G protein signaling independently of its glutamate-gated channel function, suggesting GLR-3 as a metabotropic cold receptor. The vertebrate GLR-3 homolog GluK2 from zebrafish, mouse, and human can all function as a cold receptor in heterologous systems. Mouse DRG sensory neurons ex- prc GluK2, and GluK2 knockdown in these neurons suppresses their sensitivity to cold but not cool temperatures. Our study identifies an evolutionarily conserved cold receptor, revealing that a central chemical receptor unexpectedly functions as a thermal receptor in the periphery.