Department of Physiology and Cell Information Systems, McGill University, Montreal, QC, Canada; Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada.
Department of Physics, Université de Montréal, Montreal, QC, Canada.
Cell. 2020 Mar 5;180(5):956-967.e17. doi: 10.1016/j.cell.2020.01.033. Epub 2020 Feb 20.
Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.
机械转导,即将机械刺激转化为电信号,是触觉、疼痛感知、听觉和本体感觉等基本生理功能的基础过程。尽管已经确定了其中一些功能的机制,但对疼痛感知至关重要的分子仍然难以捉摸。在这里,我们报告了 TACAN(Tmem120A)的鉴定,TACAN 是一种参与感知机械疼痛的离子通道。TACAN 表达在一组伤害感受器中,其异源表达增加细胞系中机械诱发的电流。TACAN 在合成脂质中的纯化和重建产生了功能性离子通道。最后,伤害感受器特异性诱导敲除 TACAN 降低了伤害感受器的机械敏感性,并减少了对机械性疼痛刺激的行为反应,但对热或触觉刺激没有影响。我们提出 TACAN 是一种离子通道,有助于感知机械性疼痛。