Ubiquitylation of voltage-gated sodium channels.

Détails

ID Serval
serval:BIB_3CDF6C0DA6A2
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Ubiquitylation of voltage-gated sodium channels.
Périodique
Handbook of Experimental Pharmacology
Auteur(s)
Laedermann C.J., Decosterd I., Abriel H.
ISSN
0171-2004 (Print)
ISSN-L
0171-2004
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
221
Pages
231-250
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review Publication Status: ppublish
Résumé
Ion channel proteins are regulated by different types of posttranslational modifications. The focus of this review is the regulation of voltage-gated sodium channels (Navs) upon their ubiquitylation. The amiloride-sensitive epithelial sodium channel (ENaC) was the first ion channel shown to be regulated upon ubiquitylation. This modification results from the binding of ubiquitin ligase from the Nedd4 family to a protein-protein interaction domain, known as the PY motif, in the ENaC subunits. Many of the Navs have similar PY motifs, which have been demonstrated to be targets of Nedd4-dependent ubiquitylation, tagging them for internalization from the cell surface. The role of Nedd4-dependent regulation of the Nav membrane density in physiology and disease remains poorly understood. Two recent studies have provided evidence that Nedd4-2 is downregulated in dorsal root ganglion (DRG) neurons in both rat and mouse models of nerve injury-induced neuropathic pain. Using two different mouse models, one with a specific knockout of Nedd4-2 in sensory neurons and another where Nedd4-2 was overexpressed with the use of viral vectors, it was demonstrated that the neuropathy-linked neuronal hyperexcitability was the result of Nav1.7 and Nav1.8 overexpression due to Nedd4-2 downregulation. These studies provided the first in vivo evidence of the role of Nedd4-2-dependent regulation of Nav channels in a disease state. This ubiquitylation pathway may be involved in the development of symptoms and diseases linked to Nav-dependent hyperexcitability, such as pain, cardiac arrhythmias, epilepsy, migraine, and myotonias.
Mots-clé
Action Potentials, Animals, Endosomal Sorting Complexes Required for Transport/chemistry, Endosomal Sorting Complexes Required for Transport/metabolism, Epithelial Sodium Channels/chemistry, Epithelial Sodium Channels/metabolism, Humans, Ion Channel Gating, Protein Binding, Protein Interaction Domains and Motifs, Protein Isoforms, Signal Transduction, Sodium/metabolism, Ubiquitin-Protein Ligases/chemistry, Ubiquitin-Protein Ligases/metabolism, Ubiquitination, Voltage-Gated Sodium Channels/chemistry, Voltage-Gated Sodium Channels/metabolism
Pubmed
Création de la notice
08/09/2014 13:29
Dernière modification de la notice
20/08/2019 14:33
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