Kindlin-1

Function of Kindlin-1 in Periodontal Disease

Periodontal disease affects a large portion of the adult population. Many genetic defects in immune system functions are associated with severe periodontal disease. There are, however, only a few genetic defects that affect the structural proteins of periodontal tissues and make individuals carrying mutations susceptible to early-onset periodontal disease. These molecular defects provide clues to the normal functions of these proteins in periodontal tissues and help us to understand host defense dependent on tissue-specific proteins. We hypothesized based on findings on a single case that individuals with Kindler syndrome may be susceptible to developing periodontal disease (Wiebe et al., 1996). In a larger study population, we have recently discovered that Kindler syndrome is associated with early onset periodontal disease (Wiebe et al., 2003). Individuals with this syndrome present with a blistering skin disease phenotype of unknown etiology until recently. We and others have shown that the defect in Kindler syndrome is localized in the lamina lucida of the basement membranes, as blisters occur at this level (Wiebe et al., 1998). Interestingly, the mutation in practically all Kindler patients was localized to a novel intracellular protein named kindlin-1. Kindlin-1 is a C. elegans homologue that is located in focal contacts and is believed to be involved in organization of the actin cytoskeleton. Based on molecular homology, kindlin-1 could potentially interact with several proteins in intracellular complexes that provide linkage between the actin cytoskeleton and integrins mediating extracellular cell adhesion. Potential proteins in this complex include ILK, Mig-2, migfilin and others. The exact function of kindlin-1 is under investigation, and how a mutation in this intracellular protein can cause structural defects making individuals susceptible to an early onset form of aggressive periodontal disease remains a mystery. The main goal of this research proposal is to unravel the functions of kindlin-1 in periodontal tissues and the molecular mechanisms behind initiation of periodontal disease associated with mutations in kindlin-1.

INVESTIGATORS

Research Associates

  • Leeni Koivisto
  • Guoqiao Jiang

Laboratory Technicians

  • Cristian Sperantia