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

Nedd4-2, a HECT-type ubiquitin-protein ligase, has been implicated in regulating several ion channels, including voltage-gated sodium (Nav) 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 uncharacterised. Using Nedd4-2 deficient mice, we demonstrate here 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. Our results provide the first physiological evidence for an essential function of Nedd4-2 in regulating Navs in the central nervous system.

Source: BJ Cell - October 24, 2013 Category: Biochemistry Authors: J A Ekberg, N A Boase, G Y Rychkov, J Manning, P Poronnik, S Kumar Tags: BJ Cell Source Type: research