Levin Michael, Thorlin Thorleif, Robinson Kenneth R, Nogi Taisaku, Mercola Mark
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell. 2002 Oct 4;111(1):77-89. doi: 10.1016/s0092-8674(02)00939-x.
A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity.
一项药理学筛选确定，H⁺和K⁺ATP酶转运蛋白对于非洲爪蟾左右体轴的正常定向至关重要。母源性H⁺/K⁺-ATP酶mRNA在单细胞非洲爪蟾胚胎中呈对称表达，但在最初的两次细胞分裂过程中发生定位，这表明受精后两小时内就产生了不对称性。尽管H⁺/K⁺-ATP酶亚基mRNA在鸡胚中呈对称定位，但原条左右两侧存在内源性H⁺/K⁺-ATP酶依赖性的膜电压电位差异。在这两个物种中，内源性H⁺/K⁺-ATP酶的药理学或遗传学扰动都会使不对称表达基因的左右模式随机化，并诱导器官异位。因此，左右不对称性的确定取决于由H⁺/K⁺-ATP酶活性产生的非常早期的离子通量差异。
