GENETICS OF DROSOPHILA ETHER A GO GO RELATED GENE POTASSIUM CHANNELS

钾(K+)通道由一大群发挥作用的蛋白质组成 在突触传递、动作电位波形和 可兴奋细胞的激发特性。与这些广泛的 振荡器(Sh)K+通道家族的特征，许多问题 关于乙醚的功能和调节仍然没有答案-a- GO-GO相关基因(ERG)产物在细胞生理学中具有重要意义 人类视网膜电信号在长QT综合征中的作用值得进一步研究 调查。假设离子通道可以控制在 转录以及受其他信号蛋白/离子的调控 Channels，我们建议在 转录水平和识别关键的反式作用因子 控制DERG的表达。此外，我们将利用遗传和 通过生物化学方法确定可能存在的关键调控分子 包括井筒通道的辅助亚单位或在上行或下行 DERG基因两侧的DERG基因组序列的调控作用。 初步证据已经定位了DERG转录控制点 在一个确定的基因组区域内，拟议的实验将有助于 确定S表达所需的关键部位以及反式作用 影响DERG基因时空表达的因素。 我们还将利用基因筛查来鉴定其他基因产品 修改DERG功能，包括辅助亚单位或调节性亚基 影响由DERG调节或调制的信号通路的分子。 因为果蝇是为数不多的能够原位遗传的生物之一 K+通道的突变分析可以与两种异源 表达和体内生理学，这些研究将使我们能够 阐明ERG K+通道功能和调控的新信息 并可能阐明ERG在细胞生理学、信号转导和 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.