The Fibril-associated Collagen IX Provides a Novel Mechanism for Cell Adhesion to Cartilaginous Matrix

Käpylä, Jarmo; Jäälinoja, Juha; Tulla, Mira; Ylöstalo, Joni; Nissinen, Liisa; Viitasalo, Tiina; Vehviläinen, Piia; Marjomäki, Varpu; Nykvist, Petri; Säämänen, Anna‐Marja; Farndale, Richard W.; Birk, David E.; Ala‐Kokko, Leena; Heino, Jyrki

doi:10.1074/jbc.m409412200

Cited by 60 publications

(37 citation statements)

References 65 publications

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“…Furthermore, because chondrocytes bear ␣10␤1 integrin more abundantly than ␣1␤1 integrin (14), a potential molecular interaction of ␣10␤1 integrin with collagen XVI needs further investigation to understand the role of collagen XVI in cellular interactions in cartilage. Another FACIT molecule, collagen IX, which is abundant in cartilage, has recently been shown to avidly interact with each of the four collagen-binding integrins (40). Together with that study, our data suggest that a general task of FACIT molecules, which decorate the D-banded collagen fibrils and other fibrillar systems, may be to contribute a linkage between these fibrillar ECM structures and the integrin receptors on cells.…”

Section: Discussionsupporting

confidence: 57%

Collagen XVI Harbors an Integrin α1β1 Recognition Site in Its C-terminal Domains

Eble

Kassner

Niland

et al. 2006

Journal of Biological Chemistry

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Collagen XVI is integrated tissue-dependently into distinct fibrillar aggregates, such as D-banded cartilage fibrils and fibrillin-1-containing microfibrils. In skin, the distribution of collagen XVI overlaps that of the collagen-binding integrins ␣1␤1 and ␣2␤1. Basal layer keratinocytes express integrin ␣2␤1, whereas integrin ␣1␤1 occurs in smooth muscle cells surrounding blood vessels, in hair follicles, and on adipocytes. Cells bearing the integrins ␣1␤1 and ␣2␤1 attach and spread on recombinant collagen XVI. Furthermore, collagen XVI induces the recruitment of these integrins into focal adhesion plaques, a principal step in integrin signaling. Of potential physiological relevance, these integrin-collagen XVI interactions may connect cells with specialized fibrils, thus contributing to the organization of fibrillar and cellular components within connective tissues. In cell-free binding assays, collagen XVI is more avidly bound by ␣1␤1 integrin than by ␣2␤1 integrin. Both integrins interact with collagen XVI via the A domain of their ␣ subunits. A tryptic collagen XVI fragment comprising the collagenous domains 1-3 is recognized by ␣1␤1 integrin. Electron microscopy of complexes of ␣1␤1 integrin with this tryptic collagen XVI fragment or with full-length collagen XVI revealed a unique ␣1␤1 integrin-binding site within collagen XVI located close to its C-terminal end.Collagen XVI belongs to the fibril-associated collagens with interrupted triple helices (FACIT) 3 family of collagens (1, 2) and is composed of 10 collagenous domains, designated as COL1-10, which are flanked by 11 noncollagenous (NC) regions (3). It constitutes a minor component of the extracellular matrices (ECM) of skin and cartilage. Despite its integration into small heterotypic D-banded fibrils of cartilage, collagen XVI is not generally a component of D-banded fibrils, which contain several types of collagens and further constituents, i.e. small leucine-rich proteoglycans and noncollagenous glycoproteins, in an alloy-like mixture (4, 5). In a tissue-specific manner, collagen XVI is incorporated into structurally and functionally discrete matrix aggregates, such as in specialized fibrillin-1-rich microfibrils in skin. Collagen XVI preferentially associates with that part of the microfibrillar apparatus lacking an amorphous elastin core and is localized in the dermal epidermal junction (DEJ) zone of the papillary dermis (4). Here the microfibrils insert perpendicularly into the basement membrane. This location suggests that collagen XVI plays an active role in anchoring microfibrils to basement membranes. Despite its occurrence in the dermis, it is not only produced by fibroblasts but also by keratinocytes, similarly to type VII collagen (6, 7). However, the mechanism by which these collagens are transported across the basement membrane and incorporated into the mesenchymal stroma is yet unknown. Although many matrix proteins self-assemble and thus contribute to the organization of supramolecular networks, cells also affect the architecture ...

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Section: Discussionsupporting

confidence: 57%

Collagen XVI Harbors an Integrin α1β1 Recognition Site in Its C-terminal Domains

Eble

Kassner

Niland

et al. 2006

Journal of Biological Chemistry

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“…The surfaces of chick embryo sternal cartilage fibrils are D-periodically (D=64 nm) studded by triple helical Col3-domains of collagen IX molecules [48]. Therefore, this region of collagen IX should be available for attachment of integrins, especially since it reportedly contains the only binding site for the I-domains of α1β1-or α2β1-integrins [49]. However, integrin binding could not be observed in this study even after treatment of the fibrils with guanidinium hydrochloride.…”

Section: Binding Of α1-or α2-integrin I-domains To Authentic Cartilagcontrasting

confidence: 39%

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

et al. 2017

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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 surfacesuprastructures 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-, α2 β1-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-containing adhesion suprastructures to the non-collagenous fibril periphery but not to the collagenous fibril cores. The biological importance of the well-investigated recognition of collagen molecules by integrins is unknown. Possible scenarios may include fibrillogenesis, fibril degradation and/orphagocytosis, recruitment of cells to remodeling sites, or molecular signaling across cytoplasmic membranes. In these circumstances, collagen molecules may lack a fibrillar organization. However, other processes requiring robust biomechanical functions, such as fibril organization in tissues, cell division, adhesion, or migration, do not involve direct integrin-collagen interactions.

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“…The cleavage removing the 50-kDa fragment could disrupt the potential binding of type IX collagen to cells, mediated by collagen receptor integrins (54), as well as to heparan sulfate proteoglycans at the cell surface.…”

Section: Table 3 Peptides Matching the Collagen ␣1 (Ix) Chainmentioning

confidence: 99%

Fragmentation of Proteins in Cartilage Treated with Interleukin-1

Danfelter

Önnerfjord

2007

Journal of Biological Chemistry

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Degradation of bovine nasal cartilage induced by interleukin-1 (IL-1) was used to study catabolic events in the tissue over 16 days. Culture medium was fractionated by two-dimensional electrophoresis (isoelectric focusing and SDS-PAGE). Identification of components by peptide mass fingerprinting revealed released fragments representing the NC4 domain of the type IX collagen ␣1 chain at days 12 and 16. A novel peptide antibody against a near N-terminal epitope of the NC4 domain confirmed the finding and indicated the presence of one of the fragments already at day 9. Mass spectrometric analysis of the two most abundant fragments revealed that the smallest one contained almost the entire NC4 domain cleaved between arginine 258 and isoleucine 259 in the sequence -ETCNELPAR 258 -COOH NH 2 -ITP-. A larger fragment contained the NC4 domain and the major part of the COL3 domain with a cleavage site between glycine 400 and threonine 401 in COL3 (-RGPPGPPGPPGPSG 400 -COOH NH 2 -TIG-). The presence of multiple collagen ␣1 (IX) N-terminal sequences demonstrates that the released molecules were cleaved at sites very close to the original N terminus either prior to or due to IL-1 treatment. Matrix metalloproteinase 13 (MMP-13) is active and cleaves fibromodulin in the time interval studied. Cartilage explants treated with MMP-13 were shown to release collagen ␣1 (IX) fragments with the same sizes and with the same cleavage sites as those obtained upon IL-1 treatment. These data describe cleavage by an MMP-13 activity toward non-collagenous and triple helix domains. These potentially important degradation events precede the major loss of type II collagen.In hyaline cartilage type IX collagen is a minor constituent of the fiber network, and type II collagen is the major constituent. The type IX collagen molecule (1) is a heterotrimer consisting of polypeptide chains ␣1, ␣2, and ␣3 (2). It belongs to the fibrilassociated collagens with interrupted triple helix. Each chain contains three triple helical (collagenous) domains, COL1, 2 -2, and -3, surrounded by four non-triple helical (non-collagenous) domains, NC1, -2, -3, and -4 ( Fig. 1) (3). The domain numbers are counted from the C terminus. Using electron microscopy, it has been shown that type IX collagen decorates the surface of type II collagen fibrils and that the NC4 domain forms a globular structure, which together with the stalklike COL3 domain protrudes out from the type II collagen fibril (4). Type IX collagen is covalently cross-linked to the type II collagen fibrils through binding to both type II collagen and other type IX collagen molecules (5-7). These bonds render extraction of type IX collagen from mature cartilage virtually impossible by agents that do not cleave peptide bonds. The NC4 domain has been shown to have an affinity for a number of molecules, for example heparin and cartilage oligomeric matrix protein (8 -10), whereas the COL domains interact with matrilin-3 (11).Mutations in the interactive cartilage oligomeric matrix protein MATN-3 and COL9 have ...

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The Fibril-associated Collagen IX Provides a Novel Mechanism for Cell Adhesion to Cartilaginous Matrix

Cited by 60 publications

References 65 publications

Collagen XVI Harbors an Integrin α1β1 Recognition Site in Its C-terminal Domains

Collagen XVI Harbors an Integrin α1β1 Recognition Site in Its C-terminal Domains

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

Fragmentation of Proteins in Cartilage Treated with Interleukin-1

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