Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization.

Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization.
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DOI:
10.1083/jcb.200612080
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发表时间:
2007-03-12
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Tsukita S
Tsukita S
中科院分区:
其他
文献类型:
--
作者:
Ikenouchi J;Umeda K;Tsukita S;Furuse M;Tsukita S

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原始粘附连接(AJs)如何在上皮极化过程中演变为空间分离的带状AJs和紧密连接(TJs)的分子机制尚未完全了解。以前,我们报道了ZO-1/ZO-2缺陷培养的上皮细胞(1[ko]/2[kd]细胞)的建立,其完全缺乏TJ。在本研究中,我们发现,带状AJs的形成显着延迟在1(ko)/2(kd)细胞在上皮极化。在1(ko)/2(kd)细胞中,原始AJ形成时Rac 1的活化严重受损。我们的数据表明,ZO-1不仅在TJ形成中起着至关重要的作用,而且通过Rac 1激活在从“成纤维细胞”AJs到带状“极化上皮”AJs的转化中也起着至关重要的作用。此外,为了检查ZO-1本身是否分别介导带状AJ和TJ形成,我们对ZO-1进行了突变分析。带状AJ和TJ形成之间对ZO-1的要求不同。我们建议,ZO-1是直接参与建立两个不同的连接域,带状AJs和TJ,在上皮极化。
The molecular mechanisms of how primordial adherens junctions (AJs) evolve into spatially separated belt-like AJs and tight junctions (TJs) during epithelial polarization are not well understood. Previously, we reported the establishment of ZO-1/ZO-2–deficient cultured epithelial cells (1[ko]/2[kd] cells), which lacked TJs completely. In the present study, we found that the formation of belt-like AJs was significantly delayed in 1(ko)/2(kd) cells during epithelial polarization. The activation of Rac1 upon primordial AJ formation is severely impaired in 1(ko)/2(kd) cells. Our data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from “fibroblastic” AJs to belt-like “polarized epithelial” AJs through Rac1 activation. Furthermore, to examine whether ZO-1 itself mediate belt-like AJ and TJ formation, respectively, we performed a mutational analysis of ZO-1. The requirement for ZO-1 differs between belt-like AJ and TJ formation. We propose that ZO-1 is directly involved in the establishment of two distinct junctional domains, belt-like AJs and TJs, during epithelial polarization.
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