美国密歇根大学X.Z. Shawn Xu研究组与中国华中科技大学Jianfeng Liu研究组合作发现一个由谷氨酸受体基因编码的寒冷感知受体。2019年8月29日，《细胞》在线发表了这一最新研究成果。

为了寻找寒冷感知受体的分子身份，研究人员对秀丽隐杆线虫中的寒冷感知突变体进行了无偏倚的遗传筛选，并分离出了glr-3基因的突变等位基因，其编码红藻氨酸型谷氨酸受体。尽管已知谷氨酸受体在中枢神经系统中传递化学突触信号，但研究人员发现GLR-3在外周感觉神经元ASER中感知寒冷，从而触发寒冷躲避行为。GLR-3通过G蛋白信号传递寒冷信号，与其谷氨酸门控通道功能无关，这表明GLR-3是一种代谢型寒冷受体。来自斑马鱼、小鼠和人类等脊椎动物GLR-3同源物GluK2在异源系统中都可以作为寒冷受体起作用。小鼠DRG感觉神经元表达GluK2，并且这些神经元中的GluK2敲低抑制了它们对寒冷而非凉爽温度的敏感性。

这项研究确定了一种进化上保守的寒冷受体，并揭示了一个关键的化学受体竟然意外地起到外周温度受体的作用。

附：英文原文

Title: A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene

Author: Jianke Gong, Jinzhi Liu, Elizabeth A. Ronan, Feiteng He, Wei Cai, Mahar Fatima, Wenyuan Zhang, Hankyu Lee, Zhaoyu Li, Gun-Ho Kim, Kevin P. Pipe, Bo Duan, Jianfeng Liu, X.Z. Shawn Xu

Issue&Volume: 29 August 2019

Abstract: 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 express 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.

DOI: https://doi.org/10.1016/j.cell.2019.07.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30833-5#