Nedd4-2 (NEDD4L) controls intracellular Na+ -mediated activity of voltage-gated sodium channels in primary cortical neurons

Jenny A. Ekberg, Natasha A. Boase, Grigori Rychkov, Jantina Manning, Philip Poronnik, Sharad Kumar

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Nedd4-2, a HECT (homologous with E6-associated protein Cterminus)- type ubiquitin protein ligase, has been implicated in regulating several ion channels, including Navs (voltage-gated sodium channels). In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions underwhich Nedd4-2 mediates native Nav regulation remain uncharacterized. Using Nedd4-2-deficient mice, we demonstrate in the present study that in foetal cortical neurons Nedd4-2 regulates Navs specifically in response to elevated intracellular Na+ , but does not affect steady-state Nav activity. In dorsal root ganglia neurons from the same mice, however, Nedd4-2 does not control Nav activities. The results of the present study provide the first physiological evidence for an essential function of Nedd4-2 in regulating Navs in the central nervous system.

LanguageEnglish
Pages27-31
Number of pages5
JournalBiochemical Journal
Volume457
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Neuron
  • Patch-clamp technique
  • Sodium transport
  • Ubiquitin protein ligase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ekberg, Jenny A. ; Boase, Natasha A. ; Rychkov, Grigori ; Manning, Jantina ; Poronnik, Philip ; Kumar, Sharad. / Nedd4-2 (NEDD4L) controls intracellular Na+ -mediated activity of voltage-gated sodium channels in primary cortical neurons. In: Biochemical Journal. 2014 ; Vol. 457, No. 1. pp. 27-31.
@article{663073d381e94b69a5067f53627047f9,
title = "Nedd4-2 (NEDD4L) controls intracellular Na+ -mediated activity of voltage-gated sodium channels in primary cortical neurons",
abstract = "Nedd4-2, a HECT (homologous with E6-associated protein Cterminus)- type ubiquitin protein ligase, has been implicated in regulating several ion channels, including Navs (voltage-gated sodium channels). In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions underwhich Nedd4-2 mediates native Nav regulation remain uncharacterized. Using Nedd4-2-deficient mice, we demonstrate in the present study that in foetal cortical neurons Nedd4-2 regulates Navs specifically in response to elevated intracellular Na+ , but does not affect steady-state Nav activity. In dorsal root ganglia neurons from the same mice, however, Nedd4-2 does not control Nav activities. The results of the present study provide the first physiological evidence for an essential function of Nedd4-2 in regulating Navs in the central nervous system.",
keywords = "Neuron, Patch-clamp technique, Sodium transport, Ubiquitin protein ligase",
author = "Ekberg, {Jenny A.} and Boase, {Natasha A.} and Grigori Rychkov and Jantina Manning and Philip Poronnik and Sharad Kumar",
year = "2014",
month = "1",
day = "1",
doi = "10.1042/BJ20131275",
language = "English",
volume = "457",
pages = "27--31",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

Nedd4-2 (NEDD4L) controls intracellular Na+ -mediated activity of voltage-gated sodium channels in primary cortical neurons. / Ekberg, Jenny A.; Boase, Natasha A.; Rychkov, Grigori; Manning, Jantina; Poronnik, Philip; Kumar, Sharad.

In: Biochemical Journal, Vol. 457, No. 1, 01.01.2014, p. 27-31.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nedd4-2 (NEDD4L) controls intracellular Na+ -mediated activity of voltage-gated sodium channels in primary cortical neurons

AU - Ekberg, Jenny A.

AU - Boase, Natasha A.

AU - Rychkov, Grigori

AU - Manning, Jantina

AU - Poronnik, Philip

AU - Kumar, Sharad

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Nedd4-2, a HECT (homologous with E6-associated protein Cterminus)- type ubiquitin protein ligase, has been implicated in regulating several ion channels, including Navs (voltage-gated sodium channels). In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions underwhich Nedd4-2 mediates native Nav regulation remain uncharacterized. Using Nedd4-2-deficient mice, we demonstrate in the present study that in foetal cortical neurons Nedd4-2 regulates Navs specifically in response to elevated intracellular Na+ , but does not affect steady-state Nav activity. In dorsal root ganglia neurons from the same mice, however, Nedd4-2 does not control Nav activities. The results of the present study provide the first physiological evidence for an essential function of Nedd4-2 in regulating Navs in the central nervous system.

AB - Nedd4-2, a HECT (homologous with E6-associated protein Cterminus)- type ubiquitin protein ligase, has been implicated in regulating several ion channels, including Navs (voltage-gated sodium channels). In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions underwhich Nedd4-2 mediates native Nav regulation remain uncharacterized. Using Nedd4-2-deficient mice, we demonstrate in the present study that in foetal cortical neurons Nedd4-2 regulates Navs specifically in response to elevated intracellular Na+ , but does not affect steady-state Nav activity. In dorsal root ganglia neurons from the same mice, however, Nedd4-2 does not control Nav activities. The results of the present study provide the first physiological evidence for an essential function of Nedd4-2 in regulating Navs in the central nervous system.

KW - Neuron

KW - Patch-clamp technique

KW - Sodium transport

KW - Ubiquitin protein ligase

UR - http://www.scopus.com/inward/record.url?scp=84890081657&partnerID=8YFLogxK

U2 - 10.1042/BJ20131275

DO - 10.1042/BJ20131275

M3 - Article

VL - 457

SP - 27

EP - 31

JO - Biochemical Journal

T2 - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -