GENETICS OF DROSOPHILA ETHER A GO GO RELATED GENE POTASSIUM CHANNELS

钾（K+）通道包括一大组蛋白质， 在突触传递、动作电位波形和 可兴奋细胞的放电特性。与这些广泛的 Shaker（Sh）K+通道系列的表征，许多问题 关于以太网的功能和调节仍然没有答案。 go-go相关基因（ERG）产物在细胞生理学中是令人感兴趣的， 人ERG在长QT综合征中的作用需要额外的 调查考虑到离子通道可以控制在 转录以及由其他信号蛋白/离子调节 通道，我们建议表征dERG表达在 转录水平，并确定反式作用因子的关键， dERG表达的控制。此外，我们将利用遗传和 生物化学方法来识别关键的调节分子， 包括dERG通道的辅助亚基，或者位于dERG通道的上游或下游 dERG基因侧翼的dERG基因组序列的调节作用。 初步证据已经定位了dERG转录控制位点 在一个确定的基因组区域内，所提出的实验将有助于 确定表达所需的关键位点， 负责dERG mRNA的空间和时间表达的因子。 我们还将利用基因筛选来鉴定其他基因产物， 修饰dERG功能并包含辅助亚基或调节亚基 影响由dERG调节或调节的信号通路的分子。 因为果蝇是少数几种能原位遗传 K+通道的突变分析可以与两种异源的 表达和体内生理学，这些研究将允许我们 阐明ERG K+通道功能和调节的新信息 并可能阐明ERG在细胞生理学、信号传导和细胞凋亡中的作用。 它在LQT综合征等疾病的病理生理学中的作用， 癫痫

Potassium (K+) channels comprise a large group of proteins that play integral roles in synaptic transmission, action potential waveform and firing properties of excitable cells. In contrast to these extensive characterization of the Shaker (Sh) K+ channel family, many questions remain unanswered concerning the function and regulation of the ether-a- go-go related gene (ERG) product in cellular physiology is of interest and the role of human ERG in Long QT syndrome warrants additional investigation. Given that ion channels can be controlled at the level of transcription as well as modulated by other signalling proteins/ion channels, we are proposing to characterize dERG expression at the transcriptional level and identify trans-acting factors key in the control of dERG expression. In addition, we will utilize genetic and biochemical approaches to identify key regulatory molecules that may comprise accessory subunits of the dERG channel or are up- or downstream modulatory effects of the dERG genomic sequence flanking the dERG gene. Preliminary evidence has localized the dERG transcriptional control sites within a define genomic region and the proposed experiments will serve to identify key sites required for expression s well as the trans-acting factors responsible for spatial and temporal expression of the dERG mRNA. We will also utilize genetic screens to identify other gene products that modify dERG function and comprise either accessory subunits or regulatory molecules that affect signaling pathways regulated or modulated by dERG. Because Drosophila is one of very few organisms in which in situ genetic mutational analysis of K+ channels can be combined with both heterologous expression and in vivo physiology, these studies will permit us to elucidate new information regarding ERG K+ channel function and regulation and may shed light upon the role of ERG in cell physiology, signaling and its role in the pathophysiology of such maladies as LQT syndrome and epilepsy.