Wang Lingxin, Du Yuzhe, Nomura Yoshiko, Dong Ke
Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI 48823, USA.
Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI 48823, USA.
Insect Biochem Mol Biol. 2015 May;60:24-32. doi: 10.1016/j.ibmb.2015.02.006. Epub 2015 Mar 2.
The Drosophila melanogaster TipE protein is thought to be an insect sodium channel auxiliary subunit functionally analogous to the β subunits of mammalian sodium channels. Besides TipE, four TipE-homologous proteins (TEH1-4) have been identified. It has been reported that TipE and TEH1 have both common and distinct effects on the gating properties of splice variants of the Drosophila sodium channel, DmNav. However, limited information is available on the effects of TEH2, TEH3 and TEH4 on the function of DmNav channel variants. In this study, we found that TEH2 increased the amplitude of peak current, but did not alter the gating properties of three examined DmNav splice variants expressed in Xenopus oocytes. In contrast, TEH4 had no effect on peak current, yet altered the gating properties of all three channel variants. Furthermore, TEH4 enhanced persistent current and slowed sodium current decay. The effects of TEH3 on DmNav variants are similar to those of TEH4, but the data were collected from a small portion of oocytes because co-expression of TEH3 with DmNav variants generated a large leak current in the majority of oocytes examined. In addition, TEH3 and TEH4 enhanced the expression of endogenous currents in oocytes. Taken together, our results reveal distinct roles of TEH proteins in modulating the function of sodium channels and suggest that TEH proteins might provide an important layer of regulation of membrane excitability in vivo. Our results also raise an intriguing possibility of TEH3/TEH4 as auxiliary subunits of other voltage-gated ion channels besides sodium channels.
黑腹果蝇TipE蛋白被认为是一种昆虫钠通道辅助亚基，在功能上类似于哺乳动物钠通道的β亚基。除了TipE，还鉴定出了四种与TipE同源的蛋白（TEH1 - 4）。据报道，TipE和TEH1对果蝇钠通道DmNav剪接变体的门控特性既有共同作用，也有不同作用。然而，关于TEH2、TEH3和TEH4对DmNav通道变体功能影响的信息有限。在本研究中，我们发现TEH2增加了峰值电流的幅度，但未改变在非洲爪蟾卵母细胞中表达的三种检测到的DmNav剪接变体的门控特性。相反，TEH4对峰值电流没有影响，但改变了所有三种通道变体的门控特性。此外，TEH4增强了持续电流并减缓了钠电流衰减。TEH3对DmNav变体的影响与TEH4相似，但由于在大多数检测的卵母细胞中，TEH3与DmNav变体共表达产生了大量泄漏电流，所以数据是从一小部分卵母细胞中收集的。此外，TEH3和TEH4增强了卵母细胞中内向电流的表达。综上所述，我们的结果揭示了TEH蛋白在调节钠通道功能中的不同作用，并表明TEH蛋白可能在体内提供了一层重要的膜兴奋性调节机制。我们的结果还提出了一个有趣的可能性，即TEH3/TEH4可能是除钠通道外其他电压门控离子通道的辅助亚基。
