A role of the transient receptor potential domain of vanilloid receptor I in channel Gating
A role of the transient receptor potential domain of vanilloid receptor I in channel Gating
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DOI：
10.1523/jneurosci.2457-07.2007
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发表时间：
2007-10-24
影响因子：
5.3
通讯作者：
Ferrer-Montiel, Antonio
中科院分区：
文献类型：
--
作者：
Garcia-Sanz, Nuria;Valente, Pierluigi;Ferrer-Montiel, Antonio
瞬时受体电位香草受体亚型1 （TRPV1）是一种可被温度和化学刺激激活的离子性受体。通道门附近的c端区域被认为是TRP结构域，是受体组装的分子决定因素。然而，这个胞内结构域在通道功能中的作用仍然是难以捉摸的。在这里，我们发现TRPV1的TRP结构域被TRPV通道的同源区域（TRPV2-TRPV6）取代不会影响受体的组装和向细胞表面的运输，尽管那些含有远亲TRPV5和TRPV6的TRP结构域的受体没有显示离子通道活性。值得注意的是，功能性嵌合体表现出对激活刺激的敏感性受损，这与该蛋白结构域对通道功能的重要贡献一致。与TRPV1不同的是，在没有辣椒素和/或热量的情况下，嵌合通道的电压依赖性门控不能被检测到。功能性嵌合体的生物物理分析表明，TRP结构域似乎是通道门控激活能的分子决定因素。总之，这些发现揭示了TRP结构域在通道门附近亚基间相互作用中的作用，这些相互作用有助于刺激感知与通道打开的耦合。
Transient receptor potential vanilloid receptor subtype 1 (TRPV1) is an ionotropic receptor activated by temperature and chemical stimuli. The C-terminal region that is adjacent to the channel gate, recognized as the TRP domain, is a molecular determinant of receptor assembly. However, the role of this intracellular domain in channel function remains elusive. Here, we show that replacement of the TRP domain of TRPV1 with the cognate region of TRPV channels (TRPV2-TRPV6) did not affect receptor assembly and trafficking to the cell surface, although those receptors containing the TRP domain of the distantly related TRPV5 and TRPV6 did not display ion channel activity. Notably, functional chimeras exhibited an impaired sensitivity to the activating stimuli, consistent with a significant contribution of this protein domain to channel function. At variance with TRPV1, voltage-dependent gating of chimeric channels could not be detected in the absence of capsaicin and/or heat. Biophysical analysis of functional chimeras revealed that the TRP domain appears to act as a molecular determinant of the activation energy of channel gating. Together, these findings uncover a role of the TRP domain in intersubunit interactions near the channel gate that contribute to the coupling of stimulus sensing to channel opening.