Ussar Siegfried, Wang Hao-Ven, Linder Stefan, Fässler Reinhard, Moser Markus
Max-Planck-Institute of Biochemistry, Department of Molecular Medicine, D-82152 Martinsried, Germany.
Exp Cell Res. 2006 Oct 1;312(16):3142-51. doi: 10.1016/j.yexcr.2006.06.030. Epub 2006 Jun 29.
The three Kindlins are a novel family of focal adhesion proteins. The Kindlin-1 (URP1) gene is mutated in Kindler syndrome, the first skin blistering disease affecting actin attachment in basal keratinocytes. Kindlin-2 (Mig-2), the best studied member of this family, binds ILK and Migfilin, which links Kindlin-2 to the actin cytoskeleton. Kindlin-3 is expressed in hematopoietic cells. Here we describe the genomic organization, gene expression and subcellular localization of murine Kindlins-1 to -3. In situ hybridizations showed that Kindlin-1 is preferentially expressed in epithelia, and Kindlin-2 in striated and smooth muscle cells. Kindlins-1 and -2 are both expressed in the epidermis. While both localize to integrin-mediated adhesion sites in cultured keratinocytes Kindlin-2, but not Kindlin-1, colocalizes with E-cadherin to cell-cell contacts in differentiated keratinocytes. Using a Kindlin-3-specific antiserum and an EGFP-tagged Kindlin-3 construct, we could show that Kindlin-3 is present in the F-actin surrounding ring structure of podosomes, which are specialized adhesion structures of hematopoietic cells.
三种Kindlin蛋白是一类新的粘着斑蛋白家族。Kindlin-1(URP1)基因在Kindler综合征中发生突变,Kindler综合征是第一种影响基底角质形成细胞中肌动蛋白附着的皮肤水疱病。Kindlin-2(Mig-2)是该家族中研究最深入的成员,它与整合素连接激酶(ILK)和Migfilin结合,从而将Kindlin-2与肌动蛋白细胞骨架联系起来。Kindlin-3在造血细胞中表达。在此,我们描述了小鼠Kindlin-1至-3的基因组结构、基因表达和亚细胞定位。原位杂交显示,Kindlin-1优先在上皮中表达,而Kindlin-2在横纹肌和平滑肌细胞中表达。Kindlin-1和-2均在表皮中表达。虽然二者在培养的角质形成细胞中均定位于整合素介导的粘附位点,但在分化的角质形成细胞中,Kindlin-2而非Kindlin-1与E-钙粘蛋白共定位于细胞间接触部位。使用一种Kindlin-3特异性抗血清和一个带有增强绿色荧光蛋白(EGFP)标签的Kindlin-3构建体,我们能够证明Kindlin-3存在于足体的F-肌动蛋白环绕环结构中,足体是造血细胞特化的粘附结构。