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H⁺/K⁺-ATP酶和细胞膜电位的不对称性是左右模式形成的一个非常早期的步骤。

Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning.

作者信息

Levin Michael, Thorlin Thorleif, Robinson Kenneth R, Nogi Taisaku, Mercola Mark

机构信息

Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

出版信息

Cell. 2002 Oct 4;111(1):77-89. doi: 10.1016/s0092-8674(02)00939-x.

Abstract

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.

摘要

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。

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