Overexpression of the Xenopus tight-junction protein claudin causes randomization of the left-right body axis

Overexpression of the Xenopus tight-junction protein claudin causes randomization of the left-right body axis
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DOI:
10.1006/dbio.2000.0116
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发表时间:
2001-02-15
影响因子:
2.7
通讯作者:
De Robertis, EM
De Robertis, EM
中科院分区:
生物学3区
文献类型:
--
作者:
Brizuela, BJ;Wessely, O;De Robertis, EM

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这项研究展示了非洲爪蛙Claudin(XclA),这是一种紧密连接蛋白,在早期发育的卵子和神经外胚层前体中大量表达。它是通过对非洲爪哇囊胚中富含微粒体的mRNAs的差异筛选而分离出来的。XclA蛋白含有四个跨膜区和一个羧基末端的细胞质区域,推测有一个与PDZ结合的部位。我们证明了XclA的这个PDZ结合位点对于它在细胞膜上的正确定位是至关重要的,并且截断形式会导致紧密连接蛋白ZO-1的非局部化。XclA的过度表达会导致卵裂球细胞黏附特性的改变,并导致内脏部位的随机化。结果表明,左右轴向模式对细胞-细胞相互作用调节的变化非常敏感,并在确定左右不对称性时涉及紧密连接蛋白。(C)2001年学术出版社。
This study presents Xenopus claudin (Xcla), a tight-junction protein that is abundantly expressed in eggs and neuroectodermal precursors during early development. It was isolated via a differential screen for mRNAs enriched in microsomes in the Xenopus blastula. The Xcla protein contains four transmembrane domains and a carboxy-terminal cytoplasmic region with a putative PDZ-binding site. We show that this PDZ-binding site of Xcla is critical for its correct localization on the cell membrane and that a truncated form leads to delocalization of the tight-junction protein ZO-1. Overexpression of Xcla causes changes in the cell adhesion properties of blastomeres and leads to visceral situs randomization. The results suggest that left-right axial patterning is very sensitive to changes in regulation of cell-cell interactions and implicate a tight-junction protein in the determination of left-right asymmetry. (C) 2001 Academic Press.