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 () and Irina Vetter ()
Additional contact information
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
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
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
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
Sulayman D. Dib-Hajj: Yale University School of Medicine
G. Gregory Neely: University of Sydney
Thomas Durek: The University of Queensland
Irina Vetter: The University of Queensland

Nature Communications, 2023, vol. 14, issue 1, 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37963-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37963-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37963-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().