Jami, Sina;
Deuis, Jennifer R;
Klasfauseweh, Tabea;
Cheng, Xiaoyang;
Kurdyukov, Sergey;
Chung, Felicity;
Okorokov, Andrei L;
... Vetter, Irina; + view all
(2023)
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function.
Nature Communications
, 14
, Article 2442. 10.1038/s41467-023-37963-2.
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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.
| Type: | Article |
|---|---|
| Title: | Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-023-37963-2 |
| Publisher version: | http://doi.org/10.1038/s41467-023-37963-2 |
| Language: | English |
| Additional information: | © The Author(s) 2023. 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/. |
| Keywords: | Ion channels in the nervous system, Membrane proteins Permeation and transport, Plant sciences, Sodium channels |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10169143 |
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