A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels
A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels
复制标题
DOI：
10.1523/jneurosci.5080-05.2006
复制
发表时间：
2006-05-03
影响因子：
5.3
通讯作者：
Latorre, R
中科院分区：
文献类型：
--
作者：
Brauchi, S;Orta, G;Latorre, R
哺乳动物的温度传导是可能的，因为背根神经节神经元和皮肤细胞中存在一组温度依赖性瞬时受体电位（TRP）通道。已经克隆了六个热TRP通道，它们的特征都是异常高的温度敏感性（Q（10）> 10）：TRPV 1 -4是热激活的，而TRPM 8和TRPA 1是冷激活的。由于缺乏结构信息，温度调节的分子基础仍然未知。在这项研究中，我们评估了热TRP的C-末端结构域的作用，并通过使用热受体TRPV 1和冷受体TRPM 8之间的嵌合体参与热激活，其中整个C-末端结构域被切换。在这里，我们证明了C-末端结构域是模块化的，并赋予通道表型的温度敏感性，通道门控动力学，和PIP 2（磷脂酰肌醇-4，5-二磷酸）调制。因此，热TRP通道包含一个可互换的特定区域，不同于电压传感器，这使得它们能够感知温度刺激。
Temperature transduction in mammals is possible because of the presence of a set of temperature-dependent transient receptor potential ( TRP) channels in dorsal root ganglia neurons and skin cells. Six thermo-TRP channels, all characterized by their unusually high temperature sensitivity ( Q(10) > 10), have been cloned: TRPV1-4 are heat activated, whereas TRPM8 and TRPA1 are activated by cold. Because of the lack of structural information, the molecular basis for regulation by temperature remains unknown. In this study, we assessed the role of the C-terminal domain of thermo-TRPs and its involvement in thermal activation by using chimeras between the heat receptor TRPV1 and the cold receptor TRPM8, in which the entire C-terminal domain was switched. Here, we demonstrate that the C-terminal domain is modular and confers the channel phenotype regarding temperature sensitivity, channel gating kinetics, and PIP2 ( phosphatidylinositol-4,5-bisphophate) modulation. Thus, thermo-TRP channels contain an interchangeable specific region, different from the voltage sensor, which allows them to sense temperature stimuli.