title: Localization and potential function of kindlin-1 in periodontal tissues.
abstract: Kindlin-1 is an intracellular focal adhesion protein that regulates the actin cytoskeleton. Patients suffering from Kindler syndrome have a homologous mutation of the kindlin-1 gene and develop skin blisters, periodontal disease, and intestinal complications because of deficient adhesion of the basal epithelial cells. We investigated kindlin-1 localization in periodontal tissue and its functions in cultured keratinocytes and showed that kindlin-1 co-localizes with migfilin and paxillin in the basal epithelial cells of oral mucosa and in cultured keratinocytes. The kindlin-1-deficient oral mucosal tissue from a patient with Kindler syndrome showed a complete lack of paxillin and reduced migfilin immunostaining in the basal keratinocytes. Co-immunoprecipitation showed that migfilin directly interacted with kindlin-1. RNA interference-induced kindlin-1 deficiency in keratinocytes led to an altered distribution of migfilin-containing focal adhesions, reduced cell spreading, decreased cell proliferation, and decelerated cell migration. Disruption of microtubules in the kindlin-1-deficient cells further reduced cell spreading, suggesting that microtubules can partially compensate for kindlin-1 deficiency. Kindlin-1 supported mature cell-extracellular matrix adhesions of keratinocytes, as downregulation of kindlin-1 expression significantly reduced the cell-adhesion strength. In summary, kindlin-1 interacts with migfilin and plays a crucial role in actin-dependent keratinocyte cell adhesion essential for epidermal and periodontal health.
authors.affiliation: Laboratory of Periodontal Biology, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Petricca
authors.forename: Mari
authors.initials: M
authors.lastname: Leppilampi
authors.forename: Guoqiao
authors.initials: G
authors.lastname: Jiang
authors.forename: Gethin R
authors.initials: GR
authors.lastname: Owen
authors.forename: Colin
authors.initials: C
authors.lastname: Wiebe
authors.forename: Yizeng
authors.initials: Y
authors.lastname: Tu
authors.forename: Leeni
authors.initials: L
authors.lastname: Koivisto
authors.forename: Lari
authors.initials: L
authors.lastname: Häkkinen
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.forename: Hannu
authors.initials: H
authors.lastname: Larjava
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000032:analysis; D004847:Epithelial Cells / Q000473:pathology; D005109:Extracellular Matrix / Q000648:ultrastructure; D022001:Focal Adhesions / Q000648:ultrastructure; D006801:Humans; D007410:Intestinal Diseases / Q000235:genetics; D015603:Keratinocytes / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D008870:Microtubules / Q000648:ultrastructure; D009061:Mouth Mucosa / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D051419:Paxillin / Q000032:analysis; D010510:Periodontal Diseases / Q000235:genetics; D010519:Periodontium / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D034622:RNA Interference; D012873:Skin Diseases, Genetic / Q000473:pathology; D012872:Skin Diseases, Vesiculobullous / Q000235:genetics; D013577:Syndrome; D000099200:Scaffold Protein ILK
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051419:Paxillin; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C473794:FBLIM1 protein, human; C475301:FERMT1 protein, human; C477322:FERMT3 protein, human