TACAN Is an Ion Channel Involved in Sensing Mechanical Pain

Lou Beaulieu-Laroche; Marine Christin; Annmarie Donoghue; Francina Agosti; Noosha Yousefpour; Hugues Petitjean; Albena Davidova; Craig Stanton; Uzair Khan; Connor Dietz; Elise Faure; Tarheen Fatima; Amanda MacPherson; Stephanie Mouchbahani-Constance; Daniel G. Bisson; Lisbet Haglund; Jean A. Ouellet; Laura S. Stone; Jonathan Samson; Mary Jo Smith; Kjetil Ask; Alfredo Ribeiro-da-Silva; Rikard Blunck; Kate Poole; Emmanuel Bourinet; Reza Sharif-Naeini

doi:10.1016/j.cell.2020.01.033

TACAN Is an Ion Channel Involved in Sensing Mechanical Pain

Lou Beaulieu-Laroche, Marine Christin, Annmarie Donoghue, Francina Agosti, Noosha Yousefpour, Hugues Petitjean, Albena Davidova, Craig Stanton, Uzair Khan, Connor Dietz, Elise Faure, Tarheen Fatima, Amanda MacPherson, Stephanie Mouchbahani-Constance, Daniel G. Bisson, Lisbet Haglund, Jean A. Ouellet, Laura S. Stone, Jonathan Samson, Mary Jo SmithKjetil Ask, Alfredo Ribeiro-da-Silva, Rikard Blunck, Kate Poole, Emmanuel Bourinet, Reza Sharif-Naeini

Anesthesiology

Research output: Contribution to journal › Article › peer-review

100 Scopus citations

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.

Original language	English (US)
Pages (from-to)	956-967.e17
Journal	Cell
Volume	180
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2020.01.033
State	Published - Mar 5 2020

Bibliographical note

Funding Information:
This work was supported by operating grants from the Canadian Institutes of Health Research, a pilot grant from the Groupe d'Etude des Prot?ines Membranaires (GEPROM), and a salary award from the Fonds de Recherche du Quebec-Sant? (to R.S.-N.). E.B. was supported by grants from the Fondation pour la Recherche M?dicale (?quipe FRM 2015) and the Agence Nationale pour la Recherche (ANR15-CE16-0012-01 and LABEX ICST). A.R.-d.-S. was supported by an operating grant from the Canadian Institutes of Health Research (MOP-136903). K.P. was partially supported by NHMRC project grant APP1122104. M.C. and N.Y. were supported by fellowships from the Louise and Alan Edwards Foundation. L.B.-L. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (PGSD2-517068-2018). K.A. was supported by the Ontario Thoracic Society and the Canada Foundation for Innovation John R. Evans Leaders Fund (31979). L.B.-L. performed and analyzed electrophysiological recordings in heterologous cell lines and nociceptors. He also contributed to manuscript and figure preparation. M.C. performed and analyzed electrophysiological recordings in heterologous cell lines and behavior experiments. A. Donoghue performed bilayer experiments. F.A. and E.B. performed whole-cell DRG recordings. N.Y. T.F. and A.R.-d.-S. performed immunohistochemistry experiments. H.P. performed in situ hybridization and behavior experiments. A. Davidova performed in situ experiments, immunostaining, cell culture, and transfection; validated siRNA and shRNA; and generated stable cell lines. C.S. performed COS-7 recordings. U.K. and C.D. performed HEK293 recordings. E.F. performed TACAN purification experiments for bilayer recordings. A.M. performed TACAN membrane localization experiments. S.M.-C. D.G.B. L.H. J.A.O. and L.S.S. dissected human DRG from donors. J.S. provided in situ probes for human TACAN. M.-J.S. and K.A. performed ISH on human DRGs. R.B. supervised bilayer experiments. K.P. performed whole-cell TACAN experiments on pillars. R.S.-N. designed experiments, supervised the project, and prepared the manuscript. R.S.-N. has a patent (US9551718B2) related to this work.

Funding Information:
This work was supported by operating grants from the Canadian Institutes of Health Research , a pilot grant from the Groupe d’Etude des Protéines Membranaires (GEPROM), and a salary award from the Fonds de Recherche du Quebec-Santé (to R.S.-N.). E.B. was supported by grants from the Fondation pour la Recherche Médicale ( Équipe FRM 2015 ) and the Agence Nationale pour la Recherche ( ANR15-CE16-0012-01 and LABEX ICST ). A.R.-d.-S. was supported by an operating grant from the Canadian Institutes of Health Research ( MOP-136903 ). K.P. was partially supported by NHMRC project grant APP1122104 . M.C. and N.Y. were supported by fellowships from the Louise and Alan Edwards Foundation . L.B.-L. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) ( PGSD2-517068-2018 ). K.A. was supported by the Ontario Thoracic Society and the Canada Foundation for Innovation John R. Evans Leaders Fund ( 31979 ).

Publisher Copyright:
© 2020

Keywords

TACAN
bilayer
ion channel
mechanosensitive
mechanotransduction
nociceptor
pain
patch clamp
pillar
Mechanotransduction, Cellular/genetics
Nociceptors/metabolism
Pain/genetics
Humans
Stress, Mechanical
Touch/genetics
Mice, Knockout
Patch-Clamp Techniques
Animals
Ion Channels/genetics
Mice
Lipids/genetics
Gene Expression Regulation/genetics

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article

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10.1016/j.cell.2020.01.033

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Beaulieu-Laroche, L., Christin, M., Donoghue, A., Agosti, F., Yousefpour, N., Petitjean, H., Davidova, A., Stanton, C., Khan, U., Dietz, C., Faure, E., Fatima, T., MacPherson, A., Mouchbahani-Constance, S., Bisson, D. G., Haglund, L., Ouellet, J. A., Stone, L. S., Samson, J., ... Sharif-Naeini, R. (2020). TACAN Is an Ion Channel Involved in Sensing Mechanical Pain. Cell, 180(5), 956-967.e17. https://doi.org/10.1016/j.cell.2020.01.033

Beaulieu-Laroche, L, Christin, M, Donoghue, A, Agosti, F, Yousefpour, N, Petitjean, H, Davidova, A, Stanton, C, Khan, U, Dietz, C, Faure, E, Fatima, T, MacPherson, A, Mouchbahani-Constance, S, Bisson, DG, Haglund, L, Ouellet, JA, Stone, LS, Samson, J, Smith, MJ, Ask, K, Ribeiro-da-Silva, A, Blunck, R, Poole, K, Bourinet, E & Sharif-Naeini, R 2020, 'TACAN Is an Ion Channel Involved in Sensing Mechanical Pain', Cell, vol. 180, no. 5, pp. 956-967.e17. https://doi.org/10.1016/j.cell.2020.01.033

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title = "TACAN Is an Ion Channel Involved in Sensing Mechanical Pain",

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.",

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author = "Lou Beaulieu-Laroche and Marine Christin and Annmarie Donoghue and Francina Agosti and Noosha Yousefpour and Hugues Petitjean and Albena Davidova and Craig Stanton and Uzair Khan and Connor Dietz and Elise Faure and Tarheen Fatima and Amanda MacPherson and Stephanie Mouchbahani-Constance and Bisson, {Daniel G.} and Lisbet Haglund and Ouellet, {Jean A.} and Stone, {Laura S.} and Jonathan Samson and Smith, {Mary Jo} and Kjetil Ask and Alfredo Ribeiro-da-Silva and Rikard Blunck and Kate Poole and Emmanuel Bourinet and Reza Sharif-Naeini",

note = "Funding Information: This work was supported by operating grants from the Canadian Institutes of Health Research, a pilot grant from the Groupe d'Etude des Prot?ines Membranaires (GEPROM), and a salary award from the Fonds de Recherche du Quebec-Sant? (to R.S.-N.). E.B. was supported by grants from the Fondation pour la Recherche M?dicale (?quipe FRM 2015) and the Agence Nationale pour la Recherche (ANR15-CE16-0012-01 and LABEX ICST). A.R.-d.-S. was supported by an operating grant from the Canadian Institutes of Health Research (MOP-136903). K.P. was partially supported by NHMRC project grant APP1122104. M.C. and N.Y. were supported by fellowships from the Louise and Alan Edwards Foundation. L.B.-L. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (PGSD2-517068-2018). K.A. was supported by the Ontario Thoracic Society and the Canada Foundation for Innovation John R. Evans Leaders Fund (31979). L.B.-L. performed and analyzed electrophysiological recordings in heterologous cell lines and nociceptors. He also contributed to manuscript and figure preparation. M.C. performed and analyzed electrophysiological recordings in heterologous cell lines and behavior experiments. A. Donoghue performed bilayer experiments. F.A. and E.B. performed whole-cell DRG recordings. N.Y. T.F. and A.R.-d.-S. performed immunohistochemistry experiments. H.P. performed in situ hybridization and behavior experiments. A. Davidova performed in situ experiments, immunostaining, cell culture, and transfection; validated siRNA and shRNA; and generated stable cell lines. C.S. performed COS-7 recordings. U.K. and C.D. performed HEK293 recordings. E.F. performed TACAN purification experiments for bilayer recordings. A.M. performed TACAN membrane localization experiments. S.M.-C. D.G.B. L.H. J.A.O. and L.S.S. dissected human DRG from donors. J.S. provided in situ probes for human TACAN. M.-J.S. and K.A. performed ISH on human DRGs. R.B. supervised bilayer experiments. K.P. performed whole-cell TACAN experiments on pillars. R.S.-N. designed experiments, supervised the project, and prepared the manuscript. R.S.-N. has a patent (US9551718B2) related to this work. Funding Information: This work was supported by operating grants from the Canadian Institutes of Health Research , a pilot grant from the Groupe d{\textquoteright}Etude des Prot{\'e}ines Membranaires (GEPROM), and a salary award from the Fonds de Recherche du Quebec-Sant{\'e} (to R.S.-N.). E.B. was supported by grants from the Fondation pour la Recherche M{\'e}dicale ( {\'E}quipe FRM 2015 ) and the Agence Nationale pour la Recherche ( ANR15-CE16-0012-01 and LABEX ICST ). A.R.-d.-S. was supported by an operating grant from the Canadian Institutes of Health Research ( MOP-136903 ). K.P. was partially supported by NHMRC project grant APP1122104 . M.C. and N.Y. were supported by fellowships from the Louise and Alan Edwards Foundation . L.B.-L. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) ( PGSD2-517068-2018 ). K.A. was supported by the Ontario Thoracic Society and the Canada Foundation for Innovation John R. Evans Leaders Fund ( 31979 ). Publisher Copyright: {\textcopyright} 2020",

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month = mar,

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doi = "10.1016/j.cell.2020.01.033",

language = "English (US)",

volume = "180",

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T1 - TACAN Is an Ion Channel Involved in Sensing Mechanical Pain

AU - Beaulieu-Laroche, Lou

AU - Christin, Marine

AU - Donoghue, Annmarie

AU - Agosti, Francina

AU - Yousefpour, Noosha

AU - Petitjean, Hugues

AU - Davidova, Albena

AU - Stanton, Craig

AU - Khan, Uzair

AU - Dietz, Connor

AU - Faure, Elise

AU - Fatima, Tarheen

AU - MacPherson, Amanda

AU - Mouchbahani-Constance, Stephanie

AU - Bisson, Daniel G.

AU - Haglund, Lisbet

AU - Ouellet, Jean A.

AU - Stone, Laura S.

AU - Samson, Jonathan

AU - Smith, Mary Jo

AU - Ask, Kjetil

AU - Ribeiro-da-Silva, Alfredo

AU - Blunck, Rikard

AU - Poole, Kate

AU - Bourinet, Emmanuel

AU - Sharif-Naeini, Reza

N1 - Funding Information: This work was supported by operating grants from the Canadian Institutes of Health Research, a pilot grant from the Groupe d'Etude des Prot?ines Membranaires (GEPROM), and a salary award from the Fonds de Recherche du Quebec-Sant? (to R.S.-N.). E.B. was supported by grants from the Fondation pour la Recherche M?dicale (?quipe FRM 2015) and the Agence Nationale pour la Recherche (ANR15-CE16-0012-01 and LABEX ICST). A.R.-d.-S. was supported by an operating grant from the Canadian Institutes of Health Research (MOP-136903). K.P. was partially supported by NHMRC project grant APP1122104. M.C. and N.Y. were supported by fellowships from the Louise and Alan Edwards Foundation. L.B.-L. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (PGSD2-517068-2018). K.A. was supported by the Ontario Thoracic Society and the Canada Foundation for Innovation John R. Evans Leaders Fund (31979). L.B.-L. performed and analyzed electrophysiological recordings in heterologous cell lines and nociceptors. He also contributed to manuscript and figure preparation. M.C. performed and analyzed electrophysiological recordings in heterologous cell lines and behavior experiments. A. Donoghue performed bilayer experiments. F.A. and E.B. performed whole-cell DRG recordings. N.Y. T.F. and A.R.-d.-S. performed immunohistochemistry experiments. H.P. performed in situ hybridization and behavior experiments. A. Davidova performed in situ experiments, immunostaining, cell culture, and transfection; validated siRNA and shRNA; and generated stable cell lines. C.S. performed COS-7 recordings. U.K. and C.D. performed HEK293 recordings. E.F. performed TACAN purification experiments for bilayer recordings. A.M. performed TACAN membrane localization experiments. S.M.-C. D.G.B. L.H. J.A.O. and L.S.S. dissected human DRG from donors. J.S. provided in situ probes for human TACAN. M.-J.S. and K.A. performed ISH on human DRGs. R.B. supervised bilayer experiments. K.P. performed whole-cell TACAN experiments on pillars. R.S.-N. designed experiments, supervised the project, and prepared the manuscript. R.S.-N. has a patent (US9551718B2) related to this work. Funding Information: This work was supported by operating grants from the Canadian Institutes of Health Research , a pilot grant from the Groupe d’Etude des Protéines Membranaires (GEPROM), and a salary award from the Fonds de Recherche du Quebec-Santé (to R.S.-N.). E.B. was supported by grants from the Fondation pour la Recherche Médicale ( Équipe FRM 2015 ) and the Agence Nationale pour la Recherche ( ANR15-CE16-0012-01 and LABEX ICST ). A.R.-d.-S. was supported by an operating grant from the Canadian Institutes of Health Research ( MOP-136903 ). K.P. was partially supported by NHMRC project grant APP1122104 . M.C. and N.Y. were supported by fellowships from the Louise and Alan Edwards Foundation . L.B.-L. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) ( PGSD2-517068-2018 ). K.A. was supported by the Ontario Thoracic Society and the Canada Foundation for Innovation John R. Evans Leaders Fund ( 31979 ). Publisher Copyright: © 2020

PY - 2020/3/5

Y1 - 2020/3/5

N2 - 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.

AB - 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.

KW - TACAN

KW - bilayer

KW - ion channel

KW - mechanosensitive

KW - mechanotransduction

KW - nociceptor

KW - pain

KW - patch clamp

KW - pillar

KW - Mechanotransduction, Cellular/genetics

KW - Nociceptors/metabolism

KW - Pain/genetics

KW - Humans

KW - Stress, Mechanical

KW - Touch/genetics

KW - Mice, Knockout

KW - Patch-Clamp Techniques

KW - Animals

KW - Ion Channels/genetics

KW - Mice

KW - Lipids/genetics

KW - Gene Expression Regulation/genetics

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UR - http://www.scopus.com/inward/citedby.url?scp=85080124491&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2020.01.033

DO - 10.1016/j.cell.2020.01.033

M3 - Article

C2 - 32084332

AN - SCOPUS:85080124491

SN - 0092-8674

VL - 180

SP - 956-967.e17

JO - Cell

JF - Cell

IS - 5

ER -

TACAN Is an Ion Channel Involved in Sensing Mechanical Pain

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