Year: 2023
Type: article
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.
Source: Nature Communications
Authors: 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
Institutions: The University of Queensland, Institute for Molecular Bioscience, Yale University, VA Connecticut Healthcare System, The University of Sydney, Centenary Institute, University College London, Chinese Academy of Sciences, Institute of Physics, King's College London, Qatar University, Medizinische Hochschule Hannover, Australian Research Council, ARC Centre of Excellence for Innovations in Peptide and Protein Science
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: U.S. Department of Veterans Affairs, Yale University, Paralyzed Veterans of America, Wellcome Trust, Australian Cancer Research Foundation, University of Queensland, Qatar University, Department of Education and Training, Versus Arthritis, Medical Research Council, Australian Research Council, National Health and Medical Research Council, Queensland Brain Institute, Institute for Molecular Bioscience, University Of Queensland
Awards: G1082857986, G153380729, ARC Centre of Excellence for Innovations in Peptide and Protein Science, G2663690023, Toxins from Down Under: Novel tools to understand and modulate ion channels, G3171057471, G3716407161, G4431928909, National Mouse Genetics Network - NMGN - Directors flexible funding award, G5572172683, Using toxins to manipulate the gating of voltage-gated sodium channels, Pain evoked by passive transfer of IgG from fibromyalgia patients to mice, MICA ADVANTAGE visceral pain consortium: Advanced Discovery of Visceral Analgesics via Neuroimmune Targets and the Genetics of Extreme human phenotype, A reappraisal of peripheral pain pathways, Polycystin ion channels and their regulation in primary cilia, G7367294279, Accessing structurally elusive states of sodium channels as novel analgesic targets, Molecular mechanism of NAT1.7-modulated negative regulation of SCN9A expression, The role of ion channels in pain pathways
OpenAlex ID: W4367315360