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author Jami, Sina
Deuis, Jennifer R.
Klasfauseweh, Tabea
Cheng, Xiaoyang
Kurdyukov, Sergey
Chung, Felicity
Okorokov, Andrei L.
Li, Shengnan
Zhang, Jiangtao
Cristofori-Armstrong, Ben
Israel, Mathilde R.
Ju, Robert J.
Robinson, Samuel D.
Zhao, Peng
Ragnarsson, Lotten
Andersson, Åsa
Tran, Poanna
Schendel, Vanessa
McMahon, Kirsten L.
Tran, Hue N. T.
Chin, Yanni K.-Y.
Zhu, Yifei
Liu, Junyu
Crawford, Theo
Purushothamvasan, Saipriyaa
Habib, Abdella M.
Andersson, David A.
Rash, Lachlan D.
Wood, John N.
Zhao, Jing
Stehbens, Samantha J.
Mobli, Mehdi
Leffler, Andreas
Jiang, Daohua
Cox, James J.
Waxman, Stephen G.
Dib-Hajj, Sulayman D.
Neely, G. Gregory
Durek, Thomas
Vetter, Irina
author_facet Jami, Sina
Deuis, Jennifer R.
Klasfauseweh, Tabea
Cheng, Xiaoyang
Kurdyukov, Sergey
Chung, Felicity
Okorokov, Andrei L.
Li, Shengnan
Zhang, Jiangtao
Cristofori-Armstrong, Ben
Israel, Mathilde R.
Ju, Robert J.
Robinson, Samuel D.
Zhao, Peng
Ragnarsson, Lotten
Andersson, Åsa
Tran, Poanna
Schendel, Vanessa
McMahon, Kirsten L.
Tran, Hue N. T.
Chin, Yanni K.-Y.
Zhu, Yifei
Liu, Junyu
Crawford, Theo
Purushothamvasan, Saipriyaa
Habib, Abdella M.
Andersson, David A.
Rash, Lachlan D.
Wood, John N.
Zhao, Jing
Stehbens, Samantha J.
Mobli, Mehdi
Leffler, Andreas
Jiang, Daohua
Cox, James J.
Waxman, Stephen G.
Dib-Hajj, Sulayman D.
Neely, G. Gregory
Durek, Thomas
Vetter, Irina
author_sort Jami, Sina
collection PubMed
description Voltage-gated sodium (Na(V)) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na(V) channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na(V) channels, and that co-expression of TMEM233 modulates the gating properties of Na(V)1.7. These findings identify TMEM233 as a previously unknown Na(V)1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on Na(V) channel gating, and provide important insights into the function of Na(V) channels in sensory neurons.
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spelling pubmed-101479232023-04-30 Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function Jami, Sina Deuis, Jennifer R. Klasfauseweh, Tabea Cheng, Xiaoyang Kurdyukov, Sergey Chung, Felicity Okorokov, Andrei L. Li, Shengnan Zhang, Jiangtao Cristofori-Armstrong, Ben Israel, Mathilde R. Ju, Robert J. Robinson, Samuel D. Zhao, Peng Ragnarsson, Lotten Andersson, Åsa Tran, Poanna Schendel, Vanessa McMahon, Kirsten L. Tran, Hue N. T. Chin, Yanni K.-Y. Zhu, Yifei Liu, Junyu Crawford, Theo Purushothamvasan, Saipriyaa Habib, Abdella M. Andersson, David A. Rash, Lachlan D. Wood, John N. Zhao, Jing Stehbens, Samantha J. Mobli, Mehdi Leffler, Andreas Jiang, Daohua Cox, James J. Waxman, Stephen G. Dib-Hajj, Sulayman D. Neely, G. Gregory Durek, Thomas Vetter, Irina Nat Commun Article Voltage-gated sodium (Na(V)) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na(V) channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na(V) channels, and that co-expression of TMEM233 modulates the gating properties of Na(V)1.7. These findings identify TMEM233 as a previously unknown Na(V)1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on Na(V) channel gating, and provide important insights into the function of Na(V) channels in sensory neurons. Nature Publishing Group UK 2023-04-28 /pmc/articles/PMC10147923/ /pubmed/37117223 http://dx.doi.org/10.1038/s41467-023-37963-2 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jami, Sina
Deuis, Jennifer R.
Klasfauseweh, Tabea
Cheng, Xiaoyang
Kurdyukov, Sergey
Chung, Felicity
Okorokov, Andrei L.
Li, Shengnan
Zhang, Jiangtao
Cristofori-Armstrong, Ben
Israel, Mathilde R.
Ju, Robert J.
Robinson, Samuel D.
Zhao, Peng
Ragnarsson, Lotten
Andersson, Åsa
Tran, Poanna
Schendel, Vanessa
McMahon, Kirsten L.
Tran, Hue N. T.
Chin, Yanni K.-Y.
Zhu, Yifei
Liu, Junyu
Crawford, Theo
Purushothamvasan, Saipriyaa
Habib, Abdella M.
Andersson, David A.
Rash, Lachlan D.
Wood, John N.
Zhao, Jing
Stehbens, Samantha J.
Mobli, Mehdi
Leffler, Andreas
Jiang, Daohua
Cox, James J.
Waxman, Stephen G.
Dib-Hajj, Sulayman D.
Neely, G. Gregory
Durek, Thomas
Vetter, Irina
Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function
title Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function
title_full Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function
title_fullStr Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function
title_full_unstemmed Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function
title_short Pain-causing stinging nettle toxins target TMEM233 to modulate Na(V)1.7 function
title_sort pain-causing stinging nettle toxins target tmem233 to modulate na(v)1.7 function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147923/
https://www.ncbi.nlm.nih.gov/pubmed/37117223
http://dx.doi.org/10.1038/s41467-023-37963-2
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