Acquired or inherited
junctional epidermolysis bullosa are
skin diseases characterized by a separation between the epidermis and the dermis. In inherited nonlethal
junctional epidermolysis bullosa, genetic analysis has identified mutations in the COL17A1 gene coding for the transmembrane
collagen XVII whereas patients with acquired diseases have
autoantibodies against this
protein. This suggests that
collagen XVII participates in the adhesion of basal keratinocytes to the extracellular matrix. To test this hypothesis, we studied the behavior of keratinocytes with null mutations in the COL17A1 gene. Initial adhesion of mutant cells to
laminin 5 was comparable to controls and similarly dependent on alpha3beta1
integrins. The spreading of mutant cells was, however, enhanced, suggesting a propensity to migrate, which was confirmed by migration assays. In addition,
laminin 5 deposited by
collagen XVII-deficient keratinocytes was scattered and poorly organized, suggesting that correct integration of
laminin 5 within the matrix requires
collagen XVII. This assumption was supported by the co-distribution of the two
proteins in the matrix of normal human keratinocytes and by
protein-protein-binding assays showing that the C-terminus of
collagen XVII binds to
laminin 5. Together, the results unravel an unexpected role of
collagen XVII in the regulation of keratinocyte migration.