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 language | English |
---|---|
Pages (from-to) | 27-31 |
Number of pages | 5 |
Journal | Biochemical Journal |
Volume | 457 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2014 |
Externally published | Yes |