Complexes of Matrilin-1 and Biglycan or Decorin Connect Collagen VI Microfibrils to Both Collagen II and Aggrecan

Abstract

Native supramolecular assemblies containing collagen VI microfibrils and associated extracellular matrix proteins were isolated from Swarm rat chondrosarcoma tissue. Their composition and spatial organization were characterized by electron microscopy and immunological detection of molecular constituents. The small leucine-rich repeat (LRR) proteoglycans biglycan and decorin were bound to the N-terminal region of collagen VI. Chondroadherin, another member of the LRR family, was identified both at the N and C termini of collagen VI. Matrilin-1, -3, and -4 were found in complexes with biglycan or decorin at the N terminus. The interactions between collagen VI, biglycan, decorin, and matrilin-1 were studied in detail and revealed a biglycan/matrilin-1 or decorin/matrilin-1 complex acting as a linkage between collagen VI microfibrils and aggrecan or alternatively collagen II. The complexes between matrilin-1 and biglycan or decorin were also reconstituted in vitro. Colocalization of collagen VI and the different ligands in the pericellular matrix of cultured chondrosarcoma cells supported the physiological relevance of the observed interactions in matrix assembly.Connective tissues are characterized by an abundant extracellular matrix in which a wide variety of different proteins and proteoglycans assemble into multimolecular complexes, often in the form of networks. The fibrillar collagens are major components (for review, see Ref. 1) and, in cartilage, collagen II forms cross-striated fibrils in association with collagen IX and XI (2). Collagen VI is another member of the collagen family that distinguishes itself by containing large globular domains at its N and C termini (3-6). The molecule consists of three genetically distinct ␣-chains, ␣1(VI), ␣2(VI), and ␣3(VI). The N-terminal globular region is composed of nine or ten von Willebrand factor (vWF) 1 A-like domains derived from the ␣3-chain. Collagen VI molecules associate laterally in an antiparallel fashion into dimers that are stabilized by disulfide bridges (3, 4, 7). The dimers aggregate further into tetramers that are secreted into the extracellular matrix (7), where they join end to end into microfibrils. These subsequently form characteristic thin beaded filaments that are found in a variety of tissues (3,8,9). The formation of microfibrils was recently shown to depend on the N5 vWFA-like domain of ␣3(VI) (10). In addition to the collagens, the large hyaluronan-binding proteoglycan, aggrecan is a major constituent of the cartilage extracellular matrix. The aggrecan core protein has a molecular weight of ϳ220 kDa (11) These major constituents provide the basic organization of the extracellular matrix, while other molecules modulate its assembly and structure. The matrilins are a family of oligomeric matrix proteins containing common structural motifs such as vWFA-like domains, epidermal growth factor-like EGF modules and coiled-coil regions (reviewed in Ref. 18). Matrilin-1 (also known as cartilage matrix protein, CMP), and matrilin-3 are abundant in ca...

Extracellular matrix in the trabecular meshwork

“…This domain also contains RGD sequences, which are responsible for cell-association. (Kielty et al 1992a;Fitzgerald et al 2001;Wiberg et al 2001;Wiberg et al 2002;Wiberg et al 2003) It also interacts with a membrane-associated CSPG 4 and microfibril-associated glycoprotein (MAGP) 1. (Kreis and Vale 1999) Finally, type VI collagen exhibits a number of alternative mRNA splice variants, some of which are marked in Fig.…”

Characterization of metalloprotease cleavage products of human articular cartilage

“…Biglycan is a small proteoglycan that binds to collagen fibrils that are located at the surface of cartilage and in pericellular regions (33). In OA cartilage, a higher concentration of biglycan was reported in the deeper layers of the tissue (34).…”

Increased expression of matrilin‐3 not only in osteoarthritic articular cartilage but also in cartilage‐forming tumors, and down‐regulation of SOX9 via epidermal growth factor domain 1–dependent signaling

“…Detailed characterization of MATN3 remains elusive, however. On the one hand, MATN3 is known to interact directly with the pericellular matrix, in which it is believed to play a role in interconnecting macromolecular networks (12)(13)(14)(15). On the other hand, coated MATN3 was demonstrated to promote settling of primary human chondrocytes (PHCs) (16), suggesting that MATN3 interacts physically with cells.…”