Biological function of laminin-5 and pathogenic impact of its deficiency.

[junctional epidermolysis bullosa]

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 alpha 3 , beta 3 and gamma 2 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 alpha 6 beta 4 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 .

Diseases
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Diseases presenting "lack of this molecule in the epidermal basement membrane zone" symptom

junctional epidermolysis bullosa

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