Molecular determinants of desensitization in an ENaC/degenerin channel.

Détails

Ressource 1Télécharger: BIB_80ABCFFE2303.P001.pdf (3586.76 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_80ABCFFE2303
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Molecular determinants of desensitization in an ENaC/degenerin channel.
Périodique
Faseb Journal
Auteur(s)
Roy S., Boiteux C., Alijevic O., Liang C., Bernèche S., Kellenberger S.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
2013
Volume
27
Numéro
12
Pages
5034-5045
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Epithelial Na(+) channel (ENaC)/degenerin family members are involved in mechanosensation, blood pressure control, pain sensation, and the expression of fear. Several of these channel types display a form of desensitization that allows the channel to limit Na(+) influx during prolonged stimulation. We used site-directed mutagenesis and chemical modification, functional analysis, and molecular dynamics simulations to investigate the role of the lower palm domain of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The lower palm domains of this trimeric channel are arranged around a central vestibule, at ∼20 Å above the plasma membrane and are covalently linked to the transmembrane channel parts. We show that the lower palm domains approach one another during desensitization. Residues in the palm co-determine the pH dependence of desensitization, its kinetics, and the stability of the desensitized state. Mutations of palm residues impair desensitization by preventing the closing movement of the palm. Overexpression of desensitization-impaired channel mutants in central neurons allowed--in contrast to overexpression of wild type--a sustained signaling response to rapid pH fluctuations. We identify and describe here the function of an important regulatory domain that most likely has a conserved role in ENaC/degenerin channels.
Mots-clé
Amino Acid Sequence, Animals, Degenerin Sodium Channels/chemistry, Degenerin Sodium Channels/genetics, Epithelial Sodium Channels/chemistry, Epithelial Sodium Channels/genetics, Hydrogen-Ion Concentration, Ion Channel Gating, Molecular Dynamics Simulation, Molecular Sequence Data, Point Mutation, Protein Structure, Tertiary, Rats, Rats, Sprague-Dawley, Xenopus
Pubmed
Web of science
Création de la notice
19/02/2014 19:42
Dernière modification de la notice
20/10/2020 11:08
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