当前位置: X-MOL 学术FASEB J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
PKCε associates with the Kv3.4 channel to promote its expression in a kinase activity‐dependent manner
The FASEB Journal ( IF 4.8 ) Pub Date : 2020-12-24 , DOI: 10.1096/fj.201901877r
Benjamin M Zemel 1, 2, 3 , Lianteng Zhi 1, 2 , Eric V Brown 1, 2 , Stephen R Tymanskyj 1, 2 , Qiansheng Liang 1, 2 , Manuel Covarrubias 1, 2
Affiliation  

The voltage‐gated potassium channel Kv3.4 is a crucial regulator of nociceptive signaling in the dorsal root ganglion (DRG) and the dorsal horn of the spinal cord. Moreover, Kv3.4 dysfunction has been linked to neuropathic pain. Although kinases and phosphatases can directly modulate Kv3.4 gating, the signaling mechanisms regulating the expression and stability of the Kv3.4 protein are generally unknown. We explored a potential role of PKCε and found an unexpected interaction that has a positive effect on Kv3.4 expression. Co‐immunoprecipitation studies revealed a physical association between PKCε and Kv3.4 in both heterologous cells and rat DRG neurons. Furthermore, in contrast to the wild‐type and constitutively active forms of PKCε, expression of a catalytically inactive form of the enzyme inhibits Kv3.4 expression and membrane localization through a dominant negative effect. Co‐expression of Kv3.4 with the wild‐type, constitutively active, or catalytically inactive forms of PKCε had no significant effects on Kv3.4 gating. These results suggest that a novel physical interaction of the Kv3.4 channel with functional PKCε primarily determines its stability and localization in DRG neurons. This interaction is akin to those of previously identified accessory ion channel proteins, which could be significant in neural tissues where Kv3.4 regulates electrical signaling.

中文翻译:

PKCε 与 Kv3.4 通道结合,以激酶活性依赖的方式促进其表达

电压门控钾通道 Kv3.4 是背根神经节 (DRG) 和脊髓背角伤害性信号传导的关键调节因子。此外,Kv3.4 功能障碍与神经性疼痛有关。虽然激酶和磷酸酶可以直接调节 Kv3.4 门控,但调节 Kv3.4 蛋白表达和稳定性的信号机制通常是未知的。我们探索了 PKCε 的潜在作用,并发现了一种对 Kv3.4 表达有积极影响的意想不到的相互作用。免疫共沉淀研究揭示了异源细胞和大鼠 DRG 神经元中 PKCε 和 Kv3.4 之间的物理关联。此外,与 PKCε 的野生型和组成型活性形式相比,该酶的催化失活形式的表达会抑制 Kv3。4表达和膜定位通过显性负效应。Kv3.4 与野生型、组成型活性或催化失活形式的 PKCε 共表达对 Kv3.4 门控没有显着影响。这些结果表明,Kv3.4 通道与功能性 PKCε 的新型物理相互作用主要决定了其在 DRG 神经元中的稳定性和定位。这种相互作用类似于先前确定的辅助离子通道蛋白的相互作用,这在 Kv3.4 调节电信号的神经组织中可能很重要。具有功能性 PKCε 的 4 通道主要决定其在 DRG 神经元中的稳定性和定位。这种相互作用类似于先前确定的辅助离子通道蛋白的相互作用,这在 Kv3.4 调节电信号的神经组织中可能很重要。具有功能性 PKCε 的 4 通道主要决定其在 DRG 神经元中的稳定性和定位。这种相互作用类似于先前确定的辅助离子通道蛋白的相互作用,这在 Kv3.4 调节电信号的神经组织中可能很重要。
更新日期:2020-12-24
down
wechat
bug