Localization and potential function of kindlin-1 in periodontal tissues.

[kindler syndrome]

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 .