Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.
Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.
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孔塔突变选择性破坏 TRPV1 通道的高灵敏度热激活，但不破坏辣椒素激活
DOI：
10.1085/jgp.201110724
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Cui Y;Yang F;Cao X;Yarov-Yarovoy V;Wang K;Zheng J
辣椒素受体瞬时受体电位香草酸（TRPV）1是一种高度热敏感的离子通道。虽然TRPV1的化学活化和热活化引起类似的刺激性疼痛感，但协同活化的分子机制仍然是神秘的。特别是，温度传感器的位置以及热量和辣椒素是否有共同的激活途径是有争议的。为了解决这些基本问题，我们寻找选择性影响一种激活形式的通道突变。我们发现，删除孔转塔的前10个氨基酸显着降低了热响应幅度和移动的热激活阈值，而辣椒素激活保持不变。移除较大部分的转台会破坏通道功能。引入一个人工序列来取代缺失的区域，恢复了这些非功能性通道中敏感的辣椒素激活。然而，热激活，仍然显着受损，与电流表现出减少的热敏性的电压门控钾通道，Kv7.4的水平无法区分。我们的研究结果表明，热和辣椒素激活TRPV1的结构和机制不同的过程，和孔转塔是一个不可缺少的通道结构参与热激活过程，但不是辣椒素激活途径的一部分。热和辣椒素对TRPV1激活的协同作用可能源于两条途径在共同激活门上的会聚。
The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate.
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影响因子：
5.3
作者：
Ahern, GP;Brooks, IM;Wang, XB
通讯作者：
Wang, XB
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：
56.9
作者：
Baukrowitz, T;Yellen, G
通讯作者：
Yellen, G
影响因子：
4
作者：
Latorre, Ramon;Brauchi, Sebastian;Vargas, Guillermo
通讯作者：
Vargas, Guillermo
影响因子：
25
作者：
Grandl, Joerg;Hu, Hongzhen;Bandell, Michael;Bursulaya, Badry;Schmidt, Manuela;Petrus, Matt;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem