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.
Nedd4-2 (NEDD4L) controls intracellular Na+-mediated activity of voltage-gated sodium channels in primary cortical neurons
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Jenny A. Ekberg, Natasha A. Boase, Grigori Rychkov, Jantina Manning, Philip Poronnik, Sharad Kumar; Nedd4-2 (NEDD4L) controls intracellular Na+-mediated activity of voltage-gated sodium channels in primary cortical neurons. Biochem J 1 January 2014; 457 (1): 27–31. doi: https://doi.org/10.1042/BJ20131275
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