Kindlin-1 and-2 Have Overlapping Functions in Epithelial Cells Implications for Phenotype Modification
Kindlin-1 and-2 Have Overlapping Functions in Epithelial Cells Implications for Phenotype Modification
复制标题
DOI：
10.1016/j.ajpath.2010.11.053
复制
发表时间：
2011-03-01
影响因子：
6
通讯作者：
Has, Cristina
中科院分区：
文献类型：
--
作者：
He, Yinghong;Esser, Philipp;Has, Cristina
Kindlin是一个新的细胞内衔接蛋白家族，在含有整合素的粘着斑中。Kindlin-1和Kindlin-2在皮肤中表达，但它们是否以及如何在成人上皮细胞中合作仍然是难以捉摸的。我们揭示了kindlin-1和kindlin-2在维持上皮完整性方面的重叠作用，并表明kindlin-1缺陷细胞的表型可以通过调节kindlin-2基因表达来调节，反之亦然。实验证据通过使用表达两种kindlin（仅表达kindlin-1或kindlin-2）或不表达它们的人角质形成细胞系来提供。Kindlin-1和Kindlin-2的双重缺陷对粘着斑形成和肌动蛋白细胞骨架组织、细胞粘附、存活、定向迁移和B的活化具有显著的负面影响。整合素，而缺乏一个kindlin只显示这些功能的可变干扰。细胞运动性和细胞-细胞接触的形成特别受到缺乏kindlin-2的影响。这些结果表明，kindlin-1和kindlin-2可以在功能上相互补偿，至少部分是这样。kindlin-2表达的环境调节的发现强调了补偿的高度生理和病理意义。UV-B辐射诱导角质形成细胞中Kindlin-2的丢失。Kindlin表达的环境调节的第一个例子对Kindler综合征（一种由Kindlin-1缺陷引起的皮肤病）的表型调节有影响。(Am J Pathol 2011，178：975-982; DOI：10.1016/j.ajpath.2010.11.053）
Kindlins are a novel family of intracellular adaptor proteins in integrin-containing focal adhesions. Kindlin-1 and -2 are expressed in the skin, but whether and how they cooperate in adult epithelial cells have remained elusive. We uncovered the overlapping roles of kindlin-1 and -2 in maintaining epithelial integrity and show that the phenotype of kindlin-1-deficient cells can be modulated by regulating kindlin-2 gene expression and vice versa. The experimental evidence is provided by use of human keratinocyte cell lines that express both kindlins, just kindlin-1 or kindlin-2, or none of them. Double deficiency of kindlin-1 and -2 had significant negative effects on focal adhesion formation and actin cytoskeleton organization, cell adhesion, survival, directional migration, and activation of B., integrin, whereas deficiency of one kindlin only showed variable perturbation of these functions. Cell motility and formation of cell-cell contacts were particularly affected by lack of kindlin-2. These results predict that kindlin-1 and -2 can functionally compensate for each other, at least in part. The high physiologic and pathologic significance of the compensation was emphasized by the discovery of environmental regulation of kindlin-2 expression. UV-B irradiation induced loss of kindlin-2 in keratinocytes. This first example of environmental regulation of kindlin expression has implications for phenotype modulation in Kindler syndrome, a skin disorder caused by kindlin-1 deficiency. (Am J Pathol 2011, 178:975-982; DOI: 10.1016/j.ajpath.2010.11.053)