The Fibril-associated Collagen IX Provides a Novel Mechanism for Cell Adhesion to Cartilaginous Matrix (original) (raw)
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Matrix biology : journal of the International Society for Matrix Biology, 2017
Interactions of cells with supramolecular aggregates of the extracellular matrix (ECM) are mediated, in part, by cell surface receptors of the integrin family. These are important molecular components of cell surface-suprastructures regulating cellular activities in general. A subfamily of β1-integrins with von Willebrand-factor A-like domains (I-domains) in their α-chains can bind to collagen molecules and, therefore, are considered as important cellular mechano-receptors. Here we show that chondrocytes strongly bind to cartilage collagens in the form of individual triple helical molecules but very weakly to fibrils formed by the same molecules. We also find that chondrocyte integrins α1β1-, α2β1- and α10β1-integrins and their I-domains have the same characteristics. Nevertheless we find integrin binding to mechanically generated cartilage fibril fragments, which also comprise peripheral non-collagenous material. We conclude that cell adhesion results from binding of integrin-conta...
Selective Binding of Collagen Subtypes by Integrin α1I, α2I, and α10I Domains
Journal of Biological Chemistry, 2001
form a special subclass of cell adhesion receptors. They are all collagen receptors, and they recognize their ligands with an inserted domain (I domain) in their ␣ subunit. We have produced the human integrin ␣ 10 I domain as a recombinant protein to reveal its ligand binding specificity. In general, ␣ 10 I did recognize collagen types I-VI and laminin-1 in a Mg 2؉-dependent manner, whereas its binding to tenascin was only slightly better than to albumin. When ␣ 10 I was tested together with the ␣ 1 I and ␣ 2 I domains, all three I domains seemed to have their own collagen binding preferences. The integrin ␣ 2 I domain bound much better to fibrillar collagens (I-III) than to basement membrane type IV collagen or to beaded filament-forming type VI collagen. Integrin ␣ 1 I had the opposite binding pattern. The integrin ␣ 10 I domain was similar to the ␣ 1 I domain in that it bound very well to collagen types IV and VI. Based on the previously published atomic structures of the ␣ 1 I and ␣ 2 I domains, we modeled the structure of the ␣ 10 I domain. The comparison of the three I domains revealed similarities and differences that could potentially explain their functional differences. Mutations were introduced into the ␣I domains, and their binding to types I, IV, and VI collagen was tested. In the ␣ 2 I domain, Asp-219 is one of the amino acids previously suggested to interact directly with type I collagen. The corresponding amino acid in both the ␣ 1 I and ␣ 10 I domains is oppositely charged (Arg-218). The mutation D219R in the ␣ 2 I domain changed the ligand binding pattern to resemble that of the ␣ 1 I and ␣ 10 I domains and, vice versa, the R218D mutation in the ␣ 1 I and ␣ 10 I domains created an ␣ 2 I domain-like ligand binding pattern. Thus, all three collagen receptors appear to differ in their ability to recognize distinct collagen subtypes. The relatively small structural differences on their collagen binding surfaces may explain the functional specifics.
The EMBO Journal, 1992
Integrins can mediate the attachment of cells to collagen type I. In the present study we have investigated the possible differences in collagen type I recognition sites for the a131 and a2OI integrins. Different cyanogen bromide (CB) fragments of the al(I) collagen chain were used in cell attachment experiments with three rat cell types, defined with regard to expression of collagen binding integrins. Primary rat hepatocytes expressed acill, primary rat cardiac fibroblasts a1c31 and a2131, and Rat-i cells only a231. All three cell types expressed 01301 but this integrin did not bind to collagen-Sepharose or to immobilized collagen type I in a radioreceptor assay. Hepatocytes and cardiac fibroblasts attached to substrata coated with al(I)CB3 and al)CB8; Rat-i cells attached to oal(I)CB3 but only poorly to al(I)CB8-coated substrata. Cardiac fibroblasts and Rat-I cells spread and formed (1-integrin-containing focal adhesions when grown on substrata coated with native collagen or al(I)CB3; focal adhesions were also detected in cardiac fibroblasts cultured on al(I)CB8. The rat a1 specific monoclonal antibody 3A3 completely inhibited hepatocyte attachment to al(I)CB3 and al(I)CB8, as well as the attachment of cardiac fibroblasts to al(I)CB8, but only partially inhibited the attachment of cardiac fibroblasts to al()CB3. 3A3 IgG did not inhibit the attachment of Rat-i cells to collagen type I or to al(I)CB3. These data indicate that binding sites for a1f31 are present in both ail(CB3 and al(I)CB8 and that al(I)CB3, but not al(I)CB8, contains a binding site for aU21, and suggest that collagen type I contains separate binding sites for alS31 and a,31. Hepatocyte attachment to heat-denatured collagen type I was inhibited by the hexapeptide GRGDTP. It therefore appears that denaturation both destroys the integrity of conformation dependent binding sites for apri and reveals a cryptic RGD-containing site recognized by the a5013 of hepatocytes.
European Journal of Biochemistry, 1989
Type IX collagen is found in hyaline cartilage, where it is associated with type I1 collagen in quarter-staggered collagen fibrils. Chicken type IX collagen has been extensively characterized and shown to contain molecules with three triple-helical domains, interspersed with non-triple-helical sequences. The molecule contains three, genetically distinct, subunits and one of these subunits carries a covalently bound glycosaminoglycan side chain.