TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.,Cell

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TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.
Cell ( IF 45.5 ) Pub Date : 2020-02-17 , DOI: 10.1016/j.cell.2020.01.033
Lou Beaulieu-Laroche ₁ , Marine Christin ₁ , Annmarie Donoghue ₂ , Francina Agosti ₃ , Noosha Yousefpour ₄ , Hugues Petitjean ₁ , Albena Davidova ₁ , Craig Stanton ₁ , Uzair Khan ₅ , Connor Dietz ₅ , Elise Faure ₆ , Tarheen Fatima ₁ , Amanda MacPherson ₅ , Stephanie Mouchbahani-Constance ₁ , Daniel G Bisson ₇ , Lisbet Haglund ₇ , Jean A Ouellet ₈ , Laura S Stone ₉ , Jonathan Samson ₁₀ , Mary-Jo Smith ₁₁ , Kjetil Ask ₁₂ , Alfredo Ribeiro-da-Silva ₄ , Rikard Blunck ₁₃ , Kate Poole ₁₄ , Emmanuel Bourinet ₃ , Reza Sharif-Naeini ₁

Affiliation

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.
Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
Department of Physiology and Cell Information Systems, McGill University, Montreal, QC, Canada.
Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.
Orthopaedic Research Laboratory, Division of Orthopaedic Surgery, McGill University, Montreal, QC, Canada; Shriners' Hospital for Children, Montreal, QC, Canada.
Shriners' Hospital for Children, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, McGill University, Montreal, QC, Canada.
Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada; Faculty of Dentistry, McGill University, Montreal, QC, Canada.
Advanced Cell Diagnostics, Newark, Toronto, ON, Canada.
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
Department of Medicine, Firestone Institute for Respiratory Health and McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
Department of Physics, Université de Montréal, Montreal, QC, Canada; Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.

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.

中文翻译：

TACAN是涉及传感机械疼痛的离子通道。

机械转导是将机械刺激转换为电信号的过程，是基础生理过程的基本过程，这些基础生理过程包括触摸和疼痛感测，听力和本体感觉。尽管已经确定了其中一些功能的机制，但对于疼痛感而言必不可少的分子仍然难以捉摸。在这里，我们报告对TACAN（Tmem120A）的鉴定，它是一种参与感知机械疼痛的离子通道。TACAN在伤害感受器的子集中表达，其异源表达增加细胞系中机械诱发的电流。合成脂质中TACAN的纯化和重建产生功能性离子通道。最后，TACAN的伤害感受器特异性诱导敲除可降低伤害感受器的机械敏感性，并减少对疼痛机械刺激的行为反应，但对热刺激或触觉刺激的反应却不明显。我们建议TACAN是有助于感知机械疼痛的离子通道。

更新日期：2020-02-20

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