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* Institut de Biologie et Chimie des Protéines, Unité Propre de Recherche 412 du Centre National de la Recherche Scientifique,
associée à l'Université Lyon I, 69367 Lyon Cedex 07, France; Mutational analyses of genes that encode
components of the anchoring complex underlying the
basolateral surface of external epithelia indicate that
this structure is the major element providing for resistance to external friction. Ultrastructurally, laminin 5 (
The Cutaneous Biology Research Center, Massachusetts General
Hospital and Harvard Medical School, Charlestown, Massachusetts 02129; § Institut de Biologie Structurale, J.P. Ebel, Grenoble
CEDEX 38027, France; and
Shriners Hospital for Children, Portland, Oregon 97201
3
3
2; a component of the anchoring filament) appears as a thin filament bridging the hemidesmosome
with the anchoring fibrils. Laminin 5 binds the cell surface through hemidesmosomal integrin
6
4. However, the interaction of laminin 5 with the anchoring fibril (type VII collagen) has not been elucidated. In
this study we demonstrate that monomeric laminin 5 binds the NH2-terminal NC-1 domain of type VII collagen. The binding is dependent upon the native conformation of both laminin 5 and type VII collagen NC-1.
Laminin 6 (
3
1
1) has no detectable affinity for type
VII collagen NC-1, indicating that the binding is mediated by the
3 and/or
2 chains of laminin 5. Approximately half of the laminin 5 solubilized from human
amnion or skin is covalently complexed with laminins 6 or 7 (
3
2
1). The adduction occurs between the NH2
terminus of laminin 5 and the branch point of the short
arms of laminins 6 or 7. The results are consistent with
the presumed orientation of laminin 5, having the
COOH-terminal G domain apposed to the hemidesmosomal integrin, and the NH2-terminal domains within the lamina densa. The results also support a model predicting that monomeric laminin 5 constitutes the anchoring filaments and bridges integrin
6
4 with type
VII collagen, and the laminin 5-6/7 complexes are
present within the interhemidesmosomal spaces bound
at least by integrin
3
1 where they may mediate basement membrane assembly or stability, but contribute
less significantly to epithelial friction resistance.
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