Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning
Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning
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DOI：
10.1016/s0092-8674(02)00939-x
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发表时间：
2002-10-04
期刊：
影响因子：
64.5
通讯作者：
Mercola, M
中科院分区：
文献类型：
--
作者：
Levin, M;Thorlin, T;Mercola, M
药理学筛选确定的H+和K+ ATP酶转运蛋白作为强制性的左右身体轴的正常方向在爪蟾。母体H+/K+-ATP酶mRNA在1-细胞非洲爪蟾胚胎中对称表达，但在前两个细胞分裂期间变得局部化，表明在受精后两小时内产生不对称。虽然H+/K+-ATP酶亚基mRNA在鸡胚中对称定位，但在原条左右两侧之间存在内源性H+/K+-ATP酶依赖的膜电位差。在这两个物种中，内源性H+/K+-ATP酶的药理学或遗传扰动使不对称表达基因的侧模式随机化并诱导器官异位。因此，LR不对称性的确定取决于一个非常早期的差分离子通量所产生的H+/K+-ATP酶活性。
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.