In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins

Jérôme Montnach, Laila Ananda Blömer, Ludivine Lopez, Luiza Filipis, Hervé Meudal, Aude Lafoux, Sébastien Nicolas, Duong Chu, Cécile Caumes, Rémy Béroud, Chris Jopling, Frank Bosmans, Corinne Huchet, Céline Landon, Marco Canepari and Michel Waard ()
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Jérôme Montnach: l’institut du thorax, INSERM, CNRS, UNIV NANTES
Laila Ananda Blömer: Laboratory of Excellence Ion Channels, Science & Therapeutics
Ludivine Lopez: l’institut du thorax, INSERM, CNRS, UNIV NANTES
Luiza Filipis: Laboratory of Excellence Ion Channels, Science & Therapeutics
Hervé Meudal: Center for Molecular Biophysics, CNRS, rue Charles Sadron, CS 80054
Aude Lafoux: Therassay Platform, IRS2-Université de Nantes
Sébastien Nicolas: l’institut du thorax, INSERM, CNRS, UNIV NANTES
Duong Chu: Queen’s University Faculty of Medicine
Cécile Caumes: Smartox Biotechnology
Rémy Béroud: Smartox Biotechnology
Chris Jopling: Institut de Génomique Fonctionnelle
Frank Bosmans: Ghent University
Corinne Huchet: Therassay Platform, IRS2-Université de Nantes
Céline Landon: Center for Molecular Biophysics, CNRS, rue Charles Sadron, CS 80054
Marco Canepari: Laboratory of Excellence Ion Channels, Science & Therapeutics
Michel Waard: l’institut du thorax, INSERM, CNRS, UNIV NANTES

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins targeting ion channels have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium (NaV) channels and validate its activity in vitro in HEK293 cells, ex vivo in brain slices and in vivo on mice neuromuscular junctions. We find that HwTxIV-Nvoc enables precise spatiotemporal control of neuronal NaV channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.

Date: 2022
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DOI: 10.1038/s41467-022-27974-w

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