Morokuma Junji, Blackiston Douglas, Levin Michael
Center for Regenerative and Developmental Biology, Forsyth Institute, Developmental Biology Department, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Cell Physiol Biochem. 2008;21(5-6):357-72. doi: 10.1159/000129628. Epub 2008 Apr 24.
Several ion transporters have been implicated in left-right (LR) patterning. Here, we characterize a new component of the early bioelectrical circuit: the potassium channel KCNQ1 and its accessory subunit KCNE1. Having cloned the native Xenopus versions of both genes, we show that both are asymmetrically localized as maternal proteins during the first few cleavages of frog embryo development in a process dependent on microtubule and actin organization. Molecular loss-of-function using dominant negative constructs demonstrates that both gene products are required for normal LR asymmetry. We propose a model whereby these channels provide an exit path for K(+) ions brought in by the H(+),K(+)-ATPase. This physiological module thus allows the obligate but electroneutral H(+),K(+)-ATPase to generate an asymmetric voltage gradient on the left and right sides. Our data reveal a new, bioelectrical component of the mechanisms patterning a large-scale axis in vertebrate embryogenesis.
几种离子转运蛋白与左右(LR)模式形成有关。在此,我们鉴定了早期生物电回路的一个新组分:钾通道KCNQ1及其辅助亚基KCNE1。在克隆了非洲爪蟾这两个基因的天然版本后,我们发现,在青蛙胚胎发育的最初几次卵裂过程中,二者作为母体蛋白不对称定位,这一过程依赖于微管和肌动蛋白的组织。使用显性负性构建体进行分子功能缺失实验表明,这两个基因产物对于正常的LR不对称都是必需的。我们提出了一个模型,即这些通道为H⁺,K⁺ - ATP酶带入的K⁺离子提供了一条出口路径。因此,这个生理模块允许专性但电中性的H⁺,K⁺ - ATP酶在左右两侧产生不对称的电压梯度。我们的数据揭示了脊椎动物胚胎发生过程中大规模轴模式形成机制的一个新的生物电组分。