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


Autoria(s): Ekberg, Jenny A; Boase, Natasha A; Rychkov, Grigori; Manning, Jantina; Poronnik, Philp; Kumar, Sharad
Data(s)

01/01/2014

Resumo

Nedd4-2, 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.

Identificador

http://eprints.qut.edu.au/68270/

Publicador

Portland Press Ltd.

Relação

DOI:10.1042/BJ20131275

Ekberg, Jenny A, Boase, Natasha A, Rychkov, Grigori, Manning, Jantina, Poronnik, Philp, & Kumar, Sharad (2014) Nedd4-2(NEDD4L) controls intracellular Na(+)-mediated activity of voltage-gated sodium channels in primary cortical neurons. Biochemical Journal, 457(1), pp. 27-31.

Fonte

School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation

Palavras-Chave #110900 NEUROSCIENCES #110999 Neurosciences not elsewhere classified #neuron, patch-clamp technique, sodium transport,
Tipo

Journal Article