TACAN Is an Ion Channel Involved in Sensing Mechanical Pain

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 ¹⁵

Abstract

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.

Keywords: TACAN; bilayer; ion channel; mechanosensitive; mechanotransduction; nociceptor; pain; patch clamp; pillar.