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Article Dans Une Revue Nature Communications Année : 2017

Voltage-gated sodium channels assemble and gate as dimers

Jérôme Clatot
  • Fonction : Auteur
Malcolm Hoshi
  • Fonction : Auteur
Xiaoping Wan
  • Fonction : Auteur
Haiyan Liu
  • Fonction : Auteur
Ankur Jain
  • Fonction : Auteur
Krekwit Shinlapawittayatorn
  • Fonction : Auteur
Eckhard Ficker
  • Fonction : Auteur
Taekjip Ha
  • Fonction : Auteur
Isabelle Deschênes
  • Fonction : Auteur

Résumé

Fast opening and closing of voltage-gated sodium channels are crucial for proper propagation of the action potential through excitable tissues. Unlike potassium channels, sodium channel α-subunits are believed to form functional monomers. Yet, an increasing body of literature shows inconsistency with the traditional idea of a single α-subunit functioning as a monomer. Here we demonstrate that sodium channel α-subunits not only physically interact with each other but they actually assemble, function and gate as a dimer. We identify the region involved in the dimerization and demonstrate that 14-3-3 protein mediates the coupled gating. Importantly we show conservation of this mechanism among mammalian sodium channels. Our study not only shifts conventional paradigms in regard to sodium channel assembly, structure, and function but importantly this discovery of the mechanism involved in channel dimerization and biophysical coupling could open the door to new approaches and targets to treat and/or prevent sodium channelopathies.
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Dates et versions

hal-01832140 , version 1 (11-07-2018)

Identifiants

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Jérôme Clatot, Malcolm Hoshi, Xiaoping Wan, Haiyan Liu, Ankur Jain, et al.. Voltage-gated sodium channels assemble and gate as dimers. Nature Communications, 2017, Equipe IIa, 8 (1), pp.2077. ⟨10.1038/s41467-017-02262-0⟩. ⟨hal-01832140⟩
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