Pain-causing stinging nettle toxins target TMEM233 to modulate Na V 1.7 function.

Autor: Jami S; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Deuis JR; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Klasfauseweh T; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Cheng X; Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Kurdyukov S; Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW, 2006, Australia., Chung F; Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW, 2006, Australia., Okorokov AL; Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK., Li S; Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK., Zhang J; Institute of Physics, Chinese Academy of Sciences, 100190, Beijing, P.R. China., Cristofori-Armstrong B; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia.; School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia., Israel MR; Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE1 1UL, London, UK., Ju RJ; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Robinson SD; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Zhao P; Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Ragnarsson L; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Andersson Å; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Tran P; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Schendel V; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., McMahon KL; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Tran HNT; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Chin YK; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia., Zhu Y; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia., Liu J; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia., Crawford T; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia., Purushothamvasan S; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia., Habib AM; College of Medicine, QU Health, Qatar University, PO Box 2713, Doha, Qatar., Andersson DA; Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE1 1UL, London, UK., Rash LD; School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia., Wood JN; Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK., Zhao J; Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK., Stehbens SJ; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Mobli M; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia., Leffler A; Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, 30625, Germany., Jiang D; Institute of Physics, Chinese Academy of Sciences, 100190, Beijing, P.R. China., Cox JJ; Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK., Waxman SG; Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Dib-Hajj SD; Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Neely GG; Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW, 2006, Australia., Durek T; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia. t.durek@imb.uq.edu.au.; Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, St Lucia, QLD, 4072, Australia. t.durek@imb.uq.edu.au., Vetter I; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia. i.vetter@uq.edu.au.; School of Pharmacy, The University of Queensland, Woolloongabba, QLD, 4102, Australia. i.vetter@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 28; Vol. 14 (1), pp. 2442. Date of Electronic Publication: 2023 Apr 28.
DOI: 10.1038/s41467-023-37963-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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