ZO1 in corneal epithelium: association to the zonula occludens and adherens junctions.

ZO1 in corneal epithelium: association to the zonula occludens and adherens junctions.
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DOI:
10.1006/exer.1996.0175
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发表时间:
1997
影响因子:
3.4
通讯作者:
Stephen P. Sugrue;J. Zieske
Stephen P. Sugrue;J. Zieske
中科院分区:
医学3区
文献类型:
--
作者:
Stephen P. Sugrue;J. Zieske

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角膜上皮与其他分层上皮一样,与单纯上皮相比,不存在良好形成的连接复合体。然而,角膜上皮的阻力屏障在很大程度上是由闭合小带(ZO,紧密连接)产生的,其形成于最顶端层的细胞之间。紧密连接在相邻上皮细胞的顶端周围提供连续密封,从而防止相邻上皮细胞之间的分子自由通过(细胞旁途径)。我们用抗紧密连接相关蛋白ZO 1的单克隆抗体检测了兔角膜上皮细胞。用这种抗体,我们解决了两种不同的模式ZO 1的表达,一个是顶端细胞的侧边界,这似乎是一个真正的小带周围的这些细胞。ZO 1的第二种表达模式是在一组点状斑点处,其对应于基底角膜上皮细胞的最顶端部分与上述翼细胞的连接。共聚焦显微镜观察表明,这些区域在与上翅细胞接触处或其附近,每个基细胞有5-6个明显的斑点。免疫电镜显示,中层上皮积累的ZO 1不是紧密连接,而是一种形式的粘附连接。ZO 1在角膜中上皮水平的表达既不与紧密连接的存在相关,也不与已建立的屏障功能相关。有趣的是,角膜上皮中的这些连接还含有桩蛋白,一种粘着斑相关磷蛋白,其是pp 125粘着斑激酶、erbB-2激酶和p21 Obcr/abl癌基因的靶点。我们推测,复层上皮,如角膜上皮内的ZO 1/桩蛋白粘附连接,可以起到加强在基底细胞到翼细胞连接的水平上的附着的作用,并通过可逆的磷酸化来调节。我们推测,桩蛋白酪氨酸残基的磷酸化调节可能在控制上皮细胞-细胞相互作用中发挥关键作用,因为它在细胞-基质粘附。
The corneal epithelium, like other stratifying epithelium, does not present a well formed junctional complex as compared to that of simple epithelia. However, the resistance barrier of the corneal epithelium is to a great extent generated by zonula occludens (ZO, tight junction), which are formed between the cells of the apical-most strata. The tight junction provides a continuous seal around the apical aspect of adjoining epithelial cells, thereby preventing the free passage of molecules between adjacent epithelial cells (paracellular pathway). We have examined rabbit corneal epithelia with monoclonal antibody against the tight junction associated protein ZO1. With this antibody, we resolved two distinct patterns of ZO1 expression, one being the lateral boundary of the apical cell, which appeared as a true zonula around these cells. The second pattern of expression for ZO1 was at a set of punctate spots that correspond to the connection of the most apical portion of the basal corneal epithelial cells, with the above wing cells. En face, confocal analyses revealed that these areas consisted of 5-6 distinct spots per basal cell at or near the contact points with the immediate wing cells above. ImmunoEM revealed that the mid-epithelial accumulations of ZO1 were not tight junctions, but rather a form of adherens junction. The expression of ZO1 in the mid-epithelial level of the cornea is neither correlated with the presence of tight junction, nor with the established barrier functions. Interestingly, these junctions in the corneal epithelium also contain paxillin, a focal adhesion associated phosphoprotein which is a target of pp125 focal adhesion kinase, erbB-2 kinase and p21Obcr/abl oncogene. We postulated that the ZO1/paxillin adherens junction within stratified epithelium, such as the corneal epithelium, may function to reinforce attachments at the level of the basal cell to wing cell junction and be regulated by reversible phosphorylation. We speculate that the regulated phosphorylation of tyrosine residues on paxillin may perform a critical role in controlling epithelial cell-cell interactions as it does in cell-matrix adhesion.