Pore region of TRPV3 ion channel is specifically required for heat activation.
Pore region of TRPV3 ion channel is specifically required for heat activation.
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DOI：
10.1038/nn.2169
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发表时间：
2008-09
影响因子：
25
通讯作者：
Patapoutian, Ardem
中科院分区：
文献类型：
--
作者：
Grandl, Joerg;Hu, Hongzhen;Bandell, Michael;Bursulaya, Badry;Schmidt, Manuela;Petrus, Matt;Patapoutian, Ardem
离子通道可以被各种刺激激活(门控)，包括化学物质、电压、机械力或温度。虽然化学物质和电压控制离子通道门控的分子机制基本上已被了解，但温度激活的逻辑仍然难以捉摸。瞬时受体电位通道TRPV3是一种非选择性阳离子通道，可被温度和樟脑等感官化学物质激活。在这里，我们筛选了∼14,000个随机突变克隆，并确定了5个单点突变，这些突变专门取消了热激活，但不干扰化学激活或电压调制。值得注意的是，所有五个突变都位于小鼠TRPV3的孔区内假定的第6个跨膜螺旋和相邻的胞外环。虽然序列不同，但我们发现青蛙TRPV3的相应环也是热激活所特需的。这个结构域从热不敏感的人TRPV2到小鼠TRPV3的交换特异性地取消了热反应，强调了这个区域对温度激活的要求。这些发现表明，TRPV3的温度敏感性与所有其他已知的激活机制是分开的，并揭示了一个与温度敏感有关的新区域。
Ion-channels can be activated (gated) by a variety of stimuli including chemicals, voltage, mechanical force or temperature. Whereas molecular mechanisms of ion-channel gating by chemicals and voltage are in principal understood, the logic of temperature-activation has remained elusive. The transient receptor potential channel TRPV3 is a non-selective cation channel activated by warm temperatures and sensory chemicals such as camphor. Here, we screened ∼14,000 random mutant clones and identified five single point-mutations that specifically abolish heat-activation, but do not perturb chemical-activation or voltage-modulation. Notably, all five mutations are located in the putative 6th transmembrane helix and the adjacent extracellular loop within the pore region of mouse TRPV3. Although distinct in sequence, we find that the corresponding loop of frog TRPV3 is also specifically required for heat-activation. The exchange of this domain from the heat-insensitive human TRPV2 into mouse TRPV3 specifically abolishes heat responses, emphasizing the requirement of this region for temperature activation. These findings demonstrate that temperature-sensitivity of TRPV3 is separable from all other known activation-mechanisms, and reveal a novel region implicated in sensing temperature.
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DOI：
10.1073/pnas.0406773101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Brauchi, S;Orio, P;Latorre, R
通讯作者：
Latorre, R
影响因子：
4
作者：
Latorre, Ramon;Brauchi, Sebastian;Vargas, Guillermo
通讯作者：
Vargas, Guillermo
影响因子：
56.9
作者：
Long, SB;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
56.9
作者：
Moqrich, A;Hwang, SW;Patapoutian, A
通讯作者：
Patapoutian, A