title: Kindlin-1 and -2 have overlapping functions in epithelial cells implications for phenotype modification.
abstract: 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 β(1) 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.
authors.affiliation: Department of Dermatology, University Medical Center Freiburg, Freiburg, Freiburg, Germany.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: He
authors.forename: Philipp
authors.initials: P
authors.lastname: Esser
authors.forename: Anja
authors.initials: A
authors.lastname: Heinemann
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Cristina
authors.initials: C
authors.lastname: Has
mesh_terms: D001768:Blister / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D048430:Cell Shape; D048429:Cell Size; D002470:Cell Survival; D004820:Epidermolysis Bullosa / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D022001:Focal Adhesions / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010510:Periodontal Diseases / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010787:Photosensitivity Disorders / Q000378:metabolism / Q000473:pathology
chemical_list: C475301:FERMT1 protein, human; C477322:FERMT3 protein, human; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins