PUBLICATION
In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins
- Authors
- Montnach, J., Blömer, L.A., Lopez, L., Filipis, L., Meudal, H., Lafoux, A., Nicolas, S., Chu, D., Caumes, C., Béroud, R., Jopling, C., Bosmans, F., Huchet, C., Landon, C., Canepari, M., De Waard, M.
- ID
- ZDB-PUB-220216-1
- Date
- 2022
- Source
- Nature communications 13: 417 (Journal)
- Registered Authors
- Jopling, Chris
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Brain/physiology
- HEK293 Cells
- Humans
- Ion Channel Gating/radiation effects
- Light*
- Mice, Inbred C57BL
- Neurons/physiology
- Neurons/radiation effects
- Peptides/chemical synthesis
- Peptides/chemistry
- Peptides/toxicity*
- Protein Engineering
- Time Factors
- Toxins, Biological/toxicity*
- Ultraviolet Rays
- Voltage-Gated Sodium Channels/metabolism*
- Zebrafish
- PubMed
- 35058427 Full text @ Nat. Commun.
Citation
Montnach, J., Blömer, L.A., Lopez, L., Filipis, L., Meudal, H., Lafoux, A., Nicolas, S., Chu, D., Caumes, C., Béroud, R., Jopling, C., Bosmans, F., Huchet, C., Landon, C., Canepari, M., De Waard, M. (2022) In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins. Nature communications. 13:417.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping