Kindlin-1 and Its Role in Kindler Syndrome

Abstract

Kindlin-1 is a member of the conserved protein family of kindlins, intracellular adaptor components of the integrin-linked adhesion sites, the focal adhesions, which serve as supramolecular signalling and actin-anchoring platforms. Together with talin, kindlins directly bind to integrin I subunit cytoplasmic tails and are responsible for integrin activation. Mutations in the kindlin-1 gene cause the Kindler syndrome, a rare genodermatosis characterised by skin blistering, photosensitivity, poikiloderma, mucosal involvement and propensity to mucocutaneous squamous cell carcinomas. Fragility and atrophy of the skin in patients with Kindler syndrome correlate with reduced adhesion and proliferation of keratinocytes in culture, but the underlying molecular pathways are not fully elucidated. Kindlin-1-deficient keratinocytes demonstrate pronounced response to stress factors, which may launch autocrine and paracrine signals and explain the dermal fibrosis and photosensitivity. A subgroup of patients with Kindler syndrome demonstrates a disseminated pattern of revertant mosaicism, which may serve as a basis for cell-based therapies.