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

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dc.contributor.authorEkberg, J.
dc.contributor.authorBoase, N.
dc.contributor.authorRychkov, G.
dc.contributor.authorManning, J.
dc.contributor.authorPoronnik, P.
dc.contributor.authorKumar, S.
dc.date.issued2014
dc.description.abstractNedd4-2, a HECT (homologous with E6-associated protein C-terminus)-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 under which 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.
dc.description.statementofresponsibilityJenny A. Ekberg, Natasha A. Boase, Grigori Rychkov, Jantina Manning, Philip Poronnik and Sharad Kumar
dc.identifier.citationBiochemical Journal, 2014; 457(1):27-31
dc.identifier.doi10.1042/BJ20131275
dc.identifier.issn0264-6021
dc.identifier.issn1470-8728
dc.identifier.orcidRychkov, G. [0000-0002-2788-2977]
dc.identifier.orcidManning, J. [0000-0001-9142-6135]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/89731
dc.language.isoen
dc.publisherPortland Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1020755
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1002863
dc.rights© The Authors Journal compilation © 2014 Biochemical Society
dc.source.urihttps://doi.org/10.1042/BJ20131275
dc.subjectneuron; patch-clamp technique; sodium transport; ubiquitin protein ligase
dc.titleNedd4-2 (NEDD4L) controls intracellular Na⁺ -mediated activity of voltage-gated sodium channels in primary cortical neurons
dc.title.alternativeNedd4-2 (NEDD4L) controls intracellular Na(+) -mediated activity of voltage-gated sodium channels in primary cortical neurons
dc.typeJournal article
pubs.publication-statusPublished

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