Differential effects of TipE and a TipE-homologous protein on modulation of gating properties of sodium channels from Drosophila melanogaster.
Differential effects of TipE and a TipE-homologous protein on modulation of gating properties of sodium channels from Drosophila melanogaster.
复制标题
DOI：
10.1371/journal.pone.0067551
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dong K
中科院分区：
文献类型：
--
作者：
Wang L;Nomura Y;Du Y;Dong K
哺乳动物钠通道的β亚基在调控哺乳动物钠通道的表达和门控中起着重要作用。然而，在昆虫中还没有β亚基的同源基因。相反，一种无关的蛋白质，在果蝇中的TipE及其在其他昆虫中的同源物，被认为是钠通道辅助亚基。此外，在黑腹毛虫中有四个TipE同源基因(TEH1-4)，在其他昆虫中有三到四个同源基因。研究表明，TipE和TEH1-3能增强非洲爪哇卵母细胞表达的各种昆虫钠通道的峰电流。然而，关于这些蛋白质如何调节钠通道的门控，特别是由选择性剪接和RNA编辑产生的钠通道变体的信息有限。在这项研究中，我们比较了TEH1和TipE对三种果蝇钠通道剪接变异体DmNav9-1、DmNav22和DmNav26在非洲爪哇卵母细胞中功能的影响。TipE和TEH1均能增强三种钠通道钠电流的幅度，加速钠电流的衰减。值得注意的是，TEH1导致所有三种变体的激活、快速失活和缓慢失活的电压依赖性超极化转变。相反，TipE没有改变这些门控属性，除了DmNav26快速失活的电压依赖关系的超极化位移。进一步分析DmNav9-1的门控动力学表明，TEH1加速了钠通道进入快速失活状态，减缓了从快失活状态和慢失活状态的恢复，从而增强了快失活和慢失活。这些结果突出了TipE和TEH1在昆虫钠通道门控中的不同作用，并表明在体内，TEH1在调节钠通道功能和神经元兴奋性方面可能比TipE发挥更广泛的作用。
β subunits of mammalian sodium channels play important roles in modulating the expression and gating of mammalian sodium channels. However, there are no orthologs of β subunits in insects. Instead, an unrelated protein, TipE in Drosophila melanogaster and its orthologs in other insects, is thought to be a sodium channel auxiliary subunit. In addition, there are four TipE-homologous genes (TEH1-4) in D. melanogaster and three to four orthologs in other insect species. TipE and TEH1-3 have been shown to enhance the peak current of various insect sodium channels expressed in Xenopus oocytes. However, limited information is available on how these proteins modulate the gating of sodium channels, particularly sodium channel variants generated by alternative splicing and RNA editing. In this study, we compared the effects of TEH1 and TipE on the function of three Drosophila sodium channel splice variants, DmNav9-1, DmNav22, and DmNav26, in Xenopus oocytes. Both TipE and TEH1 enhanced the amplitude of sodium current and accelerated current decay of all three sodium channels tested. Strikingly, TEH1 caused hyperpolarizing shifts in the voltage-dependence of activation, fast inactivation and slow inactivation of all three variants. In contrast, TipE did not alter these gating properties except for a hyperpolarizing shift in the voltage-dependence of fast inactivation of DmNav26. Further analysis of the gating kinetics of DmNav9-1 revealed that TEH1 accelerated the entry of sodium channels into the fast inactivated state and slowed the recovery from both fast- and slow-inactivated states, thereby, enhancing both fast and slow inactivation. These results highlight the differential effects of TipE and TEH1 on the gating of insect sodium channels and suggest that TEH1 may play a broader role than TipE in regulating sodium channel function and neuronal excitability in vivo.
登录
查看更多内容
影响因子：
2.5
作者：
Lin, Wei-Hsiang;Wright, Duncan E.;Baines, Richard A.
通讯作者：
Baines, Richard A.
影响因子：
3.3
作者：
Meadows, LS;Chen, YH;Ragsdale, DS
通讯作者：
Ragsdale, DS
影响因子：
3.8
作者：
Olson, Rachel O'Donnell;Liu, Zhiqi;Dong, Ke
通讯作者：
Dong, Ke
影响因子：
5.5
作者：
Balser, JR;Nuss, HB;Tomaselli, GF
通讯作者：
Tomaselli, GF
DOI：
10.1073/pnas.1208767110
发表时间：
2013-01-15
影响因子：
11.1
作者：
Brackenbury, William J.;Yuan, Yukun;Isom, Lori L.
通讯作者：
Isom, Lori L.