1998;19:94C97. and fibroblasts. This book gene item, collagen XXII, may be the initial particular extracellular matrix proteins present just at tissues junctions. Tissues integrity of most organs would depend in suprastructural aggregates containing collagens critically. The category of collagens is certainly specified in guy by 42 genes encoding TUG-770 polypeptides constructed into at least 28 specific, trimeric collagens. Their features are indirectly illustrated by a variety of human diseases caused by mutations in collagen genes. To time a lot more than 1000 different mutations are recognized to trigger collagen illnesses in a broad spectrum of body organ systems, like the skeletal program, ligaments and various other soft connective tissue, the kidney, bone tissue marrow, skin, eyesight, and as proven recently, the mind (1C3). Based on their incident in supramolecular assemblies and various other structural features, collagens are subdivided into different classes, such as TUG-770 for example fibrillar, network-forming, beaded filament-forming, fibril-associated, or transmembrane collagens. The main fibrillar collagens possess a broad tissues distribution in mesenchymal connective tissue frequently, such as bone tissue, cartilage, tendons, or dermal connective tissues (1). Nevertheless, various other collagens, the network-forming cellar membrane collagens, can display an extremely limited tissues localization coating epithelia, endothelia, or muscle tissue cells and separating them from the encompassing extracellular matrix. Such a limited expression pattern is certainly believed to reveal both an extremely specialized mechanical function in preserving integrity of the tissue area and a job in legislation of cellular features (4). The FACITs,1 fibril-associated collagens with interrupted triple helices, are quantitatively minimal collagens that frequently copolymerize into suprastructures using the main collagens and mediate ligand connections between your fibrils and their environment (5). Typically, these collagens contain triple helical and also other useful protein modules, including VWA domains and fibronectin type III-like domains. VWA domains are found in a variety of proteins, the prototype von Willebrand factor, collagens, matrilins, and integrins (for review, see Ref. 6). The general notion about the function of VWA domains is mediation of protein-protein interactions. For example, the classical collagen binding receptors, integrin 11 and 21, bind to their target via VWA domains (7). Although not yet proven, it is likely the VWA domains of FACIT collagens also bind to other proteins. Two new VWA-containing proteins, collagens XX and XXI, were recently identified by screening databases (8, 9). However, except for the gene structure and the predicted molecular domain structure, very little is known about these molecules, their distribution, or their functions in tissues. Tissue junctions have critical functions in joining tissue compartments and in transmitting forces. However, because of a lack of specific markers for TUG-770 such junctions, their molecular and cellular composition and morphogenesis have remained elusive. The only exception may be the myotendinous junction (MTJ), which represents the link between muscles and tendons, the biology and pathology of which has been studied in more detail. To overcome the drastic forces at MTJs, the muscle increases the contact area by forming finger-like interdigitations of the basement membrane zone at the junction. Some molecules are enriched but not exclusively present Rabbit polyclonal to VCL at the MTJ, integrin 71, or tenascin (10C12). Consequently, mutations in integrin 71 cause muscular dystrophy (13, 14). Recent developmental studies have provided evidence for the requirement of communication between muscle and tendon for morphogenesis. The morphogenetic origin of the muscle and tendon cells was shown to be the somites (12, 15); in muscle cell ablation experiments tendons were not formed in a muscle-less wing (16). However, except for the initial generation of the precursors, practically nothing is known about TUG-770 the signaling between the tissue compartments, which will lead to formation of the MTJ. In this study we identified and characterized a novel marker, collagen XXII (Col XXII), which exhibits a unique localization at tissue junctions in the muscle, tendons, heart, articular cartilage, and skin. EXPERIMENTAL PROCEDURES cDNA Isolation A BLAST search (17) of the data base.