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Laminin 5 binds the NC-1 domain of type VII collagen.

Rousselle P, Keene DR, Ruggiero F, Champliaud MF, Rest M, Burgeson RE - J. Cell Biol. (1997)

Bottom Line: Laminin 6 (alpha3beta1gamma1) has no detectable affinity for type VII collagen NC-1, indicating that the binding is mediated by the beta3 and/or gamma2 chains of laminin 5.Approximately half of the laminin 5 solubilized from human amnion or skin is covalently complexed with laminins 6 or 7 (alpha3beta2gamma1).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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 (alpha3beta3gamma2; 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 alpha6beta4. 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 (alpha3beta1gamma1) has no detectable affinity for type VII collagen NC-1, indicating that the binding is mediated by the beta3 and/or gamma2 chains of laminin 5. Approximately half of the laminin 5 solubilized from human amnion or skin is covalently complexed with laminins 6 or 7 (alpha3beta2gamma1). 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 alpha6beta4 with type VII collagen, and the laminin 5-6/7 complexes are present within the interhemidesmosomal spaces bound at least by integrin alpha3beta1 where they may mediate basement membrane assembly or stability, but contribute less significantly to epithelial friction resistance.

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Model for the presence of monomeric laminin 5 and  complexed laminin 5 within an epithelial–stromal junction. The  cartoon depicts monomeric laminin 5 as the bridge between  hemidesmosomal integrin α6β4 and the type VII collagen NC-1  domain. The tight binding of laminin 5 to α6β4 and to type VII  collagen provides the primary resistance to frictional forces. The  laminin 5–6/7 complex is shown within the basement membrane  between hemidesmosomes, bound by integrin α3β1 where it potentially functions to maintain basement membrane stability and  contact with the epithelial basolateral surface.
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Figure 10: Model for the presence of monomeric laminin 5 and complexed laminin 5 within an epithelial–stromal junction. The cartoon depicts monomeric laminin 5 as the bridge between hemidesmosomal integrin α6β4 and the type VII collagen NC-1 domain. The tight binding of laminin 5 to α6β4 and to type VII collagen provides the primary resistance to frictional forces. The laminin 5–6/7 complex is shown within the basement membrane between hemidesmosomes, bound by integrin α3β1 where it potentially functions to maintain basement membrane stability and contact with the epithelial basolateral surface.

Mentions: The present study indicates a second mechanism involving the binding of monomeric laminin 5 to type VII collagen NC-1 domain. These findings suggest a model (Fig. 10) that predicts that monomeric laminin 5 is the primary bridge between hemidesmosomal α6β4 and type VII collagen, and the laminin 5–6/7 complex is present within the interhemidesmosomal spaces. This model is consistent with the following observations: (a) Monomeric laminin 5 binds integrin α6β4 (Niessen et al., 1994) and type VII collagen strongly, but has minimal affinity for other basement membrane components; (b) approximately half of the extractable laminin 5 is complexed with laminins 6 and 7 (Champliaud et al., 1996); (c) the laminin 5–6/7 complex binds collagen IV strongly through nidogen (Mayer et al., 1995); (d) laminin 5 is uniformly distributed along the epithelial basement membrane (Rousselle et al., 1991), while anchoring fibrils (Ellison and Garrod, 1984) and type VII collagen (Sakai et al., 1986) are concentrated under hemidesmosomes. This model is also consistent with (e) the ultrastructure of the anchoring complex and the spatial orientation of the involved molecules (Ellison and Garrod, 1984); and (f) with the phenotypes of mutations in BPAG2 (McGrath et al., 1995; Jonkman et al., 1995), integrin β4 (Vidal et al., 1995; Dowling et al., 1996; van der Neut et al., 1996) or α6 (Georges-Labouesse et al., 1996), laminin 5 chains, and type VII collagen (Uitto et al., 1994; Bruckner-Tuderman, 1994), as the absence of laminin 5 results in the lethal Herlitz's form of epidermolysis bullosa. The absence of type VII collagen results in severe generalized dystrophic epidermolysis bullosa, and the lack of α6β4 integrin causes lethal blistering in the mouse (Dowling et al., 1996; van der Neut et al., 1996; Georges-Labouesse et al., 1996) although the absence of integrin α6β4 in humans appears to be less severe (Vidal et al., 1995). Absent mouse BPAG1 (Guo et al., 1995), BPAG2 (McGrath et al., 1995, 1996), or plectin (Gache et al., 1996; McLean et al., 1996; Smith et al., 1996) results in relatively mild blistering, suggesting that their roles in epidermal adhesion can be partially compensated by other hemidesmosomal components.


Laminin 5 binds the NC-1 domain of type VII collagen.

Rousselle P, Keene DR, Ruggiero F, Champliaud MF, Rest M, Burgeson RE - J. Cell Biol. (1997)

Model for the presence of monomeric laminin 5 and  complexed laminin 5 within an epithelial–stromal junction. The  cartoon depicts monomeric laminin 5 as the bridge between  hemidesmosomal integrin α6β4 and the type VII collagen NC-1  domain. The tight binding of laminin 5 to α6β4 and to type VII  collagen provides the primary resistance to frictional forces. The  laminin 5–6/7 complex is shown within the basement membrane  between hemidesmosomes, bound by integrin α3β1 where it potentially functions to maintain basement membrane stability and  contact with the epithelial basolateral surface.
© Copyright Policy
Related In: Results  -  Collection

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Figure 10: Model for the presence of monomeric laminin 5 and complexed laminin 5 within an epithelial–stromal junction. The cartoon depicts monomeric laminin 5 as the bridge between hemidesmosomal integrin α6β4 and the type VII collagen NC-1 domain. The tight binding of laminin 5 to α6β4 and to type VII collagen provides the primary resistance to frictional forces. The laminin 5–6/7 complex is shown within the basement membrane between hemidesmosomes, bound by integrin α3β1 where it potentially functions to maintain basement membrane stability and contact with the epithelial basolateral surface.
Mentions: The present study indicates a second mechanism involving the binding of monomeric laminin 5 to type VII collagen NC-1 domain. These findings suggest a model (Fig. 10) that predicts that monomeric laminin 5 is the primary bridge between hemidesmosomal α6β4 and type VII collagen, and the laminin 5–6/7 complex is present within the interhemidesmosomal spaces. This model is consistent with the following observations: (a) Monomeric laminin 5 binds integrin α6β4 (Niessen et al., 1994) and type VII collagen strongly, but has minimal affinity for other basement membrane components; (b) approximately half of the extractable laminin 5 is complexed with laminins 6 and 7 (Champliaud et al., 1996); (c) the laminin 5–6/7 complex binds collagen IV strongly through nidogen (Mayer et al., 1995); (d) laminin 5 is uniformly distributed along the epithelial basement membrane (Rousselle et al., 1991), while anchoring fibrils (Ellison and Garrod, 1984) and type VII collagen (Sakai et al., 1986) are concentrated under hemidesmosomes. This model is also consistent with (e) the ultrastructure of the anchoring complex and the spatial orientation of the involved molecules (Ellison and Garrod, 1984); and (f) with the phenotypes of mutations in BPAG2 (McGrath et al., 1995; Jonkman et al., 1995), integrin β4 (Vidal et al., 1995; Dowling et al., 1996; van der Neut et al., 1996) or α6 (Georges-Labouesse et al., 1996), laminin 5 chains, and type VII collagen (Uitto et al., 1994; Bruckner-Tuderman, 1994), as the absence of laminin 5 results in the lethal Herlitz's form of epidermolysis bullosa. The absence of type VII collagen results in severe generalized dystrophic epidermolysis bullosa, and the lack of α6β4 integrin causes lethal blistering in the mouse (Dowling et al., 1996; van der Neut et al., 1996; Georges-Labouesse et al., 1996) although the absence of integrin α6β4 in humans appears to be less severe (Vidal et al., 1995). Absent mouse BPAG1 (Guo et al., 1995), BPAG2 (McGrath et al., 1995, 1996), or plectin (Gache et al., 1996; McLean et al., 1996; Smith et al., 1996) results in relatively mild blistering, suggesting that their roles in epidermal adhesion can be partially compensated by other hemidesmosomal components.

Bottom Line: Laminin 6 (alpha3beta1gamma1) has no detectable affinity for type VII collagen NC-1, indicating that the binding is mediated by the beta3 and/or gamma2 chains of laminin 5.Approximately half of the laminin 5 solubilized from human amnion or skin is covalently complexed with laminins 6 or 7 (alpha3beta2gamma1).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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 (alpha3beta3gamma2; 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 alpha6beta4. 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 (alpha3beta1gamma1) has no detectable affinity for type VII collagen NC-1, indicating that the binding is mediated by the beta3 and/or gamma2 chains of laminin 5. Approximately half of the laminin 5 solubilized from human amnion or skin is covalently complexed with laminins 6 or 7 (alpha3beta2gamma1). 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 alpha6beta4 with type VII collagen, and the laminin 5-6/7 complexes are present within the interhemidesmosomal spaces bound at least by integrin alpha3beta1 where they may mediate basement membrane assembly or stability, but contribute less significantly to epithelial friction resistance.

Show MeSH
Related in: MedlinePlus