FIGURE 6.16 • Proteoglycan structure. This schematic drawing shows, on the right, a proteoglycan monomer and its relationship to the hyaluronan molecule as represented in the ground substance of cartilage. The proteoglycan monomer is composed of a core protein to which GAGs are covalently bound. The proteoglycan monomer consists of different numbers of GAGs joined to the core protein. The end of the core protein of the proteoglycan monomer interacts with a link protein, which attaches the monomer into the hyaluronan forming the proteoglycan aggregate. On the left, hyaluronan molecules forming linear aggregates, each with many proteoglycan monomers, are interwoven with a network of collagen fibrils.
case of fibroglycan or versican) or different GAG molecules (as in the case of aggrecan or syndecan).
Proteoglycans are found in the ground substance of all connective tissues and also as membrane-bound molecules on the surface of many cell types. Transmembrane proteoglycans such as syndecan link cells to ECM molecules (Fig. 6.17). For instance, syndecan is expressed two different times on the surface of B lymphocytes. Syndecan molecules are first expressed during early development when lymphocytes are attached to the matrix protein of the bone marrow as they undergo differentiation. The loss of expression of this proteoglycan coincides with the release of the B lymphocyte into the circulation. The second time the B lymphocyte expresses syndecan is during its differentiation into a plasma cell within the connective tissue. Syndecan anchors the plasma cell to the ECM proteins of the connective tissue.
Aggrecan is another important extracellular proteoglycan. Its molecules are noncovalently bound to the long molecule of hyaluronan (like bristles to the backbone in a bottle brush); this binding is facilitated by linking proteins. To each aggrecan core protein multiple chains of chondroitin sulfate and keratan sulfate are covalently attached through the trisaccharide linker. The most common proteoglycans are summarized in Table 6.4.
Multiadhesive glycoproteins play an important role in stabilizing the ECM and linking it to cell surfaces.
Multiadhesive glycoproteins represent a small but important group of proteins residing in the ECM. They are multidomain and multifunctional molecules that play an important role in stabilizing the ECM and linking it to the cell surface. They possess binding sites for a variety of ECM proteins such as collagens, proteoglycans, and GAGs; they also interact with cell-surface receptors such as integrin and laminin receptors (Fig. 6.18). Multiadhesive glycoproteins regulate and modulate functions of the ECM related to cell movement and cell migration as well as stimulate cell proliferation and differentiation. Among the best characterized multiadhesive glycoproteins are the following:  Fibronectin (250 to 280 kilodaltons) is the most abun dant glycoprotein in connective tissue. Fibronectins are
FIGURE 6.17 • Common proteoglycan monomers of the connective tissue matrix. Note the diversity of proteoglycan molecules; the number of GAGs attached to the protein core varies from one in decorin to more than 200 in aggrecan. Note also that versican has identical GAG molecules (chondroitin sulfate) attached to the core molecule whereas aggrecan has a mixture of chondroitin sulfate and keratan sulfate attached to the core protein. Syndecan is a transmembrane proteoglycan that attaches the cell membrane to the extracellular matrix.