Titus S A, Warmke J W, Ganetzky B
Laboratory of Genetics, University of Wisconsin, Madison 53706, USA.
J Neurosci. 1997 Feb 1;17(3):875-81. doi: 10.1523/JNEUROSCI.17-03-00875.1997.
The eag family of K+ channels contains three known subtypes: eag, elk, and erg. Genes representing the first two subtypes have been identified in flies and mammals, whereas the third subtype has been defined only by the human HERG gene, which encodes an inwardly rectifying channel that is mutated in some cardiac arrhythmias. To establish the predicted existence of a Drosophila gene in the erg subfamily and to learn more about the structure and biological function of channels within this subfamily, we undertook a search for the Drosophila counterpart of HERG. Here we report the isolation and characterization of the Drosophila erg gene. We show that it corresponds with the previously identified seizure (sei) locus, mutations of which cause a temperature-sensitive paralytic phenotype associated with hyperactivity in the flight motor pathway. These results yield new insights into the structure and evolution of the eag family of channels, provide a molecular explanation for the sei mutant phenotype, and demonstrate the important physiological roles of erg-type channels from invertebrates to mammals.
钾离子通道的eag家族包含三种已知的亚型:eag、elk和erg。代表前两种亚型的基因已在果蝇和哺乳动物中被鉴定出来,而第三种亚型仅由人类HERG基因定义,该基因编码一种内向整流通道,在某些心律失常中发生突变。为了确定erg亚家族中果蝇基因的预测存在,并更多地了解该亚家族中通道的结构和生物学功能,我们对HERG的果蝇对应物进行了搜索。在此,我们报告果蝇erg基因的分离和特征。我们表明它与先前鉴定的癫痫(sei)位点相对应,该位点的突变会导致与飞行运动途径中多动相关的温度敏感麻痹表型。这些结果为eag通道家族的结构和进化提供了新的见解,为sei突变体表型提供了分子解释,并证明了从无脊椎动物到哺乳动物的erg型通道的重要生理作用。