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Localization and potential function of kindlin‐1 in periodontal tissues
Author(s) -
Petricca Giorgio,
Leppilampi Mari,
Jiang Guoqiao,
Owen Gethin R.,
Wiebe Colin,
Tu Yizeng,
Koivisto Leeni,
Häkkinen Lari,
Wu Chuanyue,
Larjava Hannu
Publication year - 2009
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.2009.00651.x
Subject(s) - paxillin , microbiology and biotechnology , focal adhesion , keratinocyte , extracellular matrix , cell adhesion , biology , chemistry , cell , cell culture , signal transduction , genetics
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.