Nature Communications (Apr 2023)
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
- Sina Jami,
- Jennifer R. Deuis,
- Tabea Klasfauseweh,
- Xiaoyang Cheng,
- Sergey Kurdyukov,
- Felicity Chung,
- Andrei L. Okorokov,
- Shengnan Li,
- Jiangtao Zhang,
- Ben Cristofori-Armstrong,
- Mathilde R. Israel,
- Robert J. Ju,
- Samuel D. Robinson,
- Peng Zhao,
- Lotten Ragnarsson,
- Åsa Andersson,
- Poanna Tran,
- Vanessa Schendel,
- Kirsten L. McMahon,
- Hue N. T. Tran,
- Yanni K.-Y. Chin,
- Yifei Zhu,
- Junyu Liu,
- Theo Crawford,
- Saipriyaa Purushothamvasan,
- Abdella M. Habib,
- David A. Andersson,
- Lachlan D. Rash,
- John N. Wood,
- Jing Zhao,
- Samantha J. Stehbens,
- Mehdi Mobli,
- Andreas Leffler,
- Daohua Jiang,
- James J. Cox,
- Stephen G. Waxman,
- Sulayman D. Dib-Hajj,
- G. Gregory Neely,
- Thomas Durek,
- Irina Vetter
Affiliations
- Sina Jami
- Institute for Molecular Bioscience, The University of Queensland
- Jennifer R. Deuis
- Institute for Molecular Bioscience, The University of Queensland
- Tabea Klasfauseweh
- Institute for Molecular Bioscience, The University of Queensland
- Xiaoyang Cheng
- Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine
- Sergey Kurdyukov
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney
- Felicity Chung
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney
- Andrei L. Okorokov
- Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London
- Shengnan Li
- Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London
- Jiangtao Zhang
- Institute of Physics, Chinese Academy of Sciences
- Ben Cristofori-Armstrong
- Centre for Advanced Imaging, The University of Queensland
- Mathilde R. Israel
- Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- Robert J. Ju
- Institute for Molecular Bioscience, The University of Queensland
- Samuel D. Robinson
- Institute for Molecular Bioscience, The University of Queensland
- Peng Zhao
- Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine
- Lotten Ragnarsson
- Institute for Molecular Bioscience, The University of Queensland
- Åsa Andersson
- Institute for Molecular Bioscience, The University of Queensland
- Poanna Tran
- Institute for Molecular Bioscience, The University of Queensland
- Vanessa Schendel
- Institute for Molecular Bioscience, The University of Queensland
- Kirsten L. McMahon
- Institute for Molecular Bioscience, The University of Queensland
- Hue N. T. Tran
- Institute for Molecular Bioscience, The University of Queensland
- Yanni K.-Y. Chin
- Centre for Advanced Imaging, The University of Queensland
- Yifei Zhu
- Centre for Advanced Imaging, The University of Queensland
- Junyu Liu
- Centre for Advanced Imaging, The University of Queensland
- Theo Crawford
- Centre for Advanced Imaging, The University of Queensland
- Saipriyaa Purushothamvasan
- Centre for Advanced Imaging, The University of Queensland
- Abdella M. Habib
- College of Medicine, QU Health, Qatar University
- David A. Andersson
- Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- Lachlan D. Rash
- School of Biomedical Sciences, The University of Queensland
- John N. Wood
- Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London
- Jing Zhao
- Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London
- Samantha J. Stehbens
- Institute for Molecular Bioscience, The University of Queensland
- Mehdi Mobli
- Centre for Advanced Imaging, The University of Queensland
- Andreas Leffler
- Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School
- Daohua Jiang
- Institute of Physics, Chinese Academy of Sciences
- James J. Cox
- Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London
- Stephen G. Waxman
- Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine
- Sulayman D. Dib-Hajj
- Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine
- G. Gregory Neely
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney
- Thomas Durek
- Institute for Molecular Bioscience, The University of Queensland
- Irina Vetter
- Institute for Molecular Bioscience, The University of Queensland
- DOI
- https://doi.org/10.1038/s41467-023-37963-2
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 16
Abstract
Abstract Voltage-gated sodium (NaV) 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 NaV 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 NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons.
