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Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function

Author

Listed:
  • Sina Jami

    (The University of Queensland)

  • Jennifer R. Deuis

    (The University of Queensland)

  • Tabea Klasfauseweh

    (The University of Queensland)

  • Xiaoyang Cheng

    (Yale University School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Sergey Kurdyukov

    (University of Sydney)

  • Felicity Chung

    (University of Sydney)

  • Andrei L. Okorokov

    (University College London)

  • Shengnan Li

    (University College London)

  • Jiangtao Zhang

    (Chinese Academy of Sciences)

  • Ben Cristofori-Armstrong

    (The University of Queensland
    The University of Queensland)

  • Mathilde R. Israel

    (King’s College London)

  • Robert J. Ju

    (The University of Queensland)

  • Samuel D. Robinson

    (The University of Queensland)

  • Peng Zhao

    (Yale University School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Lotten Ragnarsson

    (The University of Queensland)

  • Åsa Andersson

    (The University of Queensland)

  • Poanna Tran

    (The University of Queensland)

  • Vanessa Schendel

    (The University of Queensland)

  • Kirsten L. McMahon

    (The University of Queensland)

  • Hue N. T. Tran

    (The University of Queensland)

  • Yanni K.-Y. Chin

    (The University of Queensland)

  • Yifei Zhu

    (The University of Queensland)

  • Junyu Liu

    (The University of Queensland)

  • Theo Crawford

    (The University of Queensland)

  • Saipriyaa Purushothamvasan

    (The University of Queensland)

  • Abdella M. Habib

    (Qatar University)

  • David A. Andersson

    (King’s College London)

  • Lachlan D. Rash

    (The University of Queensland)

  • John N. Wood

    (University College London)

  • Jing Zhao

    (University College London)

  • Samantha J. Stehbens

    (The University of Queensland)

  • Mehdi Mobli

    (The University of Queensland)

  • Andreas Leffler

    (Hannover Medical School)

  • Daohua Jiang

    (Chinese Academy of Sciences)

  • James J. Cox

    (University College London)

  • Stephen G. Waxman

    (Yale University School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Sulayman D. Dib-Hajj

    (Yale University School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • G. Gregory Neely

    (University of Sydney)

  • Thomas Durek

    (The University of Queensland
    Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science)

  • Irina Vetter

    (The University of Queensland
    The University of Queensland)

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.

Suggested Citation

  • 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. Isr, 2023. "Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37963-2
    DOI: 10.1038/s41467-023-37963-2
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    References listed on IDEAS

    as
    1. Man-Tat Lau & John Manion & Jamie B. Littleboy & Lisa Oyston & Thang M. Khuong & Qiao-Ping Wang & David T. Nguyen & Daniel Hesselson & Jamie E. Seymour & G. Gregory Neely, 2019. "Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Michael S. Minett & Mohammed A. Nassar & Anna K. Clark & Gayle Passmore & Anthony H. Dickenson & Fan Wang & Marzia Malcangio & John N. Wood, 2012. "Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    Full references (including those not matched with items on IDEAS)

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