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TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

L. Beaulieu-Laroche, M. Christin, AM Donoghue, F. Agosti, N. Yousefpour, H. Petitjean, A. Davidova, C. Stanton, U. Khan, C. Dietz, E. Faure, T. Fatima, A. MacPherson, A. Ribeiro-Da-Silva, E. Bourinet, R. Blunck, R. Sharif-Naeini
doi: https://doi.org/10.1101/338673
L. Beaulieu-Laroche
1Department of Physiology and Cell Information Systems, McGill University.
6Department of Brain & Cognitive Sciences and McGovern Institute for Brain Research, Massachusetts Institute of Technology.
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M. Christin
1Department of Physiology and Cell Information Systems, McGill University.
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AM Donoghue
2Department of Physics, Université de Montréal.
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F. Agosti
3Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
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N. Yousefpour
4Department of Pharmacology and Therapeutics, McGill University.
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H. Petitjean
1Department of Physiology and Cell Information Systems, McGill University.
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A. Davidova
1Department of Physiology and Cell Information Systems, McGill University.
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C. Stanton
1Department of Physiology and Cell Information Systems, McGill University.
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U. Khan
1Department of Physiology and Cell Information Systems, McGill University.
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C. Dietz
1Department of Physiology and Cell Information Systems, McGill University.
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E. Faure
5Department of Pharmacology and Physiology, Université de Montréal.
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T. Fatima
1Department of Physiology and Cell Information Systems, McGill University.
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A. MacPherson
1Department of Physiology and Cell Information Systems, McGill University.
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A. Ribeiro-Da-Silva
4Department of Pharmacology and Therapeutics, McGill University.
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E. Bourinet
3Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
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R. Blunck
2Department of Physics, Université de Montréal.
5Department of Pharmacology and Physiology, Université de Montréal.
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R. Sharif-Naeini
1Department of Physiology and Cell Information Systems, McGill University.
7Alan Edwards Center for Research on Pain.
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Summary

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for 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, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 07, 2018.
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TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing
L. Beaulieu-Laroche, M. Christin, AM Donoghue, F. Agosti, N. Yousefpour, H. Petitjean, A. Davidova, C. Stanton, U. Khan, C. Dietz, E. Faure, T. Fatima, A. MacPherson, A. Ribeiro-Da-Silva, E. Bourinet, R. Blunck, R. Sharif-Naeini
bioRxiv 338673; doi: https://doi.org/10.1101/338673
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TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing
L. Beaulieu-Laroche, M. Christin, AM Donoghue, F. Agosti, N. Yousefpour, H. Petitjean, A. Davidova, C. Stanton, U. Khan, C. Dietz, E. Faure, T. Fatima, A. MacPherson, A. Ribeiro-Da-Silva, E. Bourinet, R. Blunck, R. Sharif-Naeini
bioRxiv 338673; doi: https://doi.org/10.1101/338673

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