Chandy K G, Williams C B, Spencer R H, Aguilar B A, Ghanshani S, Tempel B L, Gutman G A
Department of Medicine, University of California, Irvine 92717.
Science. 1990 Feb 23;247(4945):973-5. doi: 10.1126/science.2305265.
To understand the molecular mechanisms responsible for generating physiologically diverse potassium channels in mammalian cells, mouse genomic clones have been isolated with a potassium channel complementary DNA, MBK1, that is homologous to the Drosophila potassium channel gene, Shaker. A family of three closely related potassium channel genes (MK1, MK2, and MK3) that are encoded at distinct genomic loci has been isolated. Sequence analysis reveals that the coding region of each of these three genes exists as a single uninterrupted exon in the mouse genome. This organization precludes the generation of multiple forms of the protein by alternative RNA splicing, a mechanism known to characterize the Drosophila potassium channel genes Shaker and Shab. Thus, mammals may use a different strategy for generating diverse K+ channels by encoding related genes at multiple distinct genomic loci, each of which produces only a single protein.
为了理解在哺乳动物细胞中产生生理功能多样的钾通道的分子机制,已利用与果蝇钾通道基因Shaker同源的钾通道互补DNA(MBK1)分离出小鼠基因组克隆。已分离出一个由三个紧密相关的钾通道基因(MK1、MK2和MK3)组成的家族,它们在不同的基因组位点编码。序列分析表明,这三个基因中每个基因的编码区在小鼠基因组中均作为单个不间断的外显子存在。这种结构排除了通过可变RNA剪接产生多种形式蛋白质的可能性,可变RNA剪接是一种已知的果蝇钾通道基因Shaker和Shab的特征机制。因此,哺乳动物可能通过在多个不同的基因组位点编码相关基因来采用不同的策略产生多样的K+通道,每个位点仅产生一种蛋白质。