title: Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation, and motility of epidermal keratinocytes.
abstract: A novel family of focal adhesion proteins, the kindlins, is involved in attachment of the actin cytoskeleton to the plasma membrane and in integrin-mediated cellular processes. Deficiency of kindlin-1, as a result of loss-of-function mutations in the KIND1 gene, causes Kindler syndrome, an autosomal recessive genodermatosis characterized by skin blistering, progressive skin atrophy, photosensitivity and, occasionally, carcinogenesis. Here we characterized authentic and recombinantly expressed kindlin-1 and show that it is localized in basal epidermal keratinocytes in a polar fashion, close to the cell surface facing the basement membrane, in the areas between the hemidesmosomes. We identified two forms of kindlin-1 in keratinocytes, with apparent molecular masses of 78 and 74 kDa, corresponding to phosphorylated and desphosphorylated forms of the protein. In kindlin-1-deficient skin, basal keratinocytes show multiple abnormalities: cell polarity is lost, proliferation is strongly reduced, and several cells undergo apoptosis. In vitro, deficiency of kindlin-1 in keratinocytes leads to strongly reduced cell proliferation, decreased adhesion, undirected motility, and intense protrusion activity of the plasma membrane. Taken together, these results show that kindlin-1 plays a role in keratinocyte adhesion, polarization, proliferation, and migration. It is involved in organization and anchorage of the actin cytoskeleton to integrin-associated signaling platforms.
authors.affiliation: Department of Dermatology, University Medical Center Freiburg, Hauptstrasse 7, 79104 Freiburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Herz
authors.forename: Monique
authors.initials: M
authors.lastname: Aumailley
authors.forename: Carsten
authors.initials: C
authors.lastname: Schulte
authors.forename: Ursula
authors.initials: U
authors.lastname: Schlötzer-Schrehardt
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Cristina
authors.initials: C
authors.lastname: Has
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction
chemical_list: C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins