Genetic analyses of Kindlins in mice

Article Chronology: Received 28 March 2006 Revised version received 6 June 2006 Accepted 13 June 2006 Available online 29 June 2006 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. © 2006 Elsevier Inc. All rights reserved.