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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

22 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.

Original languageEnglish
Pages (from-to)27-31
Number of pages5
JournalBiochemical Journal
Volume457
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

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