*School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4001, Australia.
Biochem J. 2014 Jan 1;457(1):27-31. doi: 10.1042/BJ20131275.
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 是一种 HECT（E6 相关蛋白 C 末端）型泛素蛋白连接酶，已被牵涉到调节多种离子通道，包括 Navs（电压门控钠离子通道）。在非洲爪蟾卵母细胞中，Nedd4-2 强烈抑制多种 Navs 的活性。然而，介导天然 Nav 调节的条件仍未被阐明。在本研究中，我们使用缺乏 Nedd4-2 的小鼠证明，在胎儿皮质神经元中，Nedd4-2 特异性地调节 Navs 以响应升高的细胞内 Na+，但不影响 Nav 的稳态活性。然而，在来自相同小鼠的背根神经节神经元中，Nedd4-2 并不控制 Nav 活性。本研究的结果为 Nedd4-2 在中枢神经系统中调节 Navs 的重要功能提供了第一个生理证据。
