The basement membrane
glycoprotein laminin-5 is a key component of the anchoring complex connecting keratinocytes to the underlying dermis. It is secreted by keratinocytes as a cross-shaped heterotrimer of alpha3, beta3 and gamma2 chains and serves as a
ligand of various transmembrane receptors, thereby regulating keratinocyte adhesion, motility and proliferation. In intact skin,
laminin-5 provides essential links to both the hemidesmosomal
alpha6beta4 integrin and the
collagen type VII molecules which form the anchoring fibrils inserting into the dermis. If the basement membrane is injured,
laminin-5 production increases rapidly. It then serves as a scaffold for cell migration, initiates the formation of hemidesmosomes and accelerates basement membrane restoration at the dermal-epidermal junction. Mutations of the
laminin-5 genes or auto-
antibodies against one of the subunits of
laminin-5 may lead to a significant lack of this molecule in the epidermal basement membrane zone. The major contributions of
laminin-5 to the resistance of the epidermis against frictional stress but also for basement membrane regeneration and repair of damaged skin are reflected by the phenotype of Herlitz
junctional epidermolysis bullosa, which is caused by an inherited absence of functional
laminin-5. This lethal disease becomes manifest in widespread blistering of skin and mucous membranes, impaired wound healing and chronic erosions containing exuberant granulation tissue. Here, we discuss current understanding of the
biological functions of
laminin-5, the pathogenic impact of its deficiency and implications on molecular approaches towards a
therapy of
junctional epidermolysis bullosa.