Not all proteoglycans are secreted components of the extracellular matrix. Some are integral components of plasma membranes and have their core protein either inserted across the lipid bilayer or attached to the lipid bilayer by a glycosylphosphatidylinositol (GPI) anchor. Among the best-characterized plasma membrane proteoglycans are the syndecans, which have a membrane-spanning core protein whose intracellular domain is thought to interact with the actin cytoskeleton and with signaling molecules in the cell cortex. Syndecans are located on the surface of many types of cells, including fibroblasts and epithelial cells. In
DECORIN AGGRECAN (MW ~40,000) (MW ~3 x 106)
Figure 19–35 The linkage between a GAG chain and its core protein in a proteoglycan molecule. a specific link tetrasaccharide is first assembled on a serine side chain. the rest of the GaG chain, consisting mainly of a repeating disaccharide unit, is then synthesized, with one sugar being added at a time. In chondroitin sulfate, the disaccharide is composed of D-glucuronic acid and N-acetyl-D-galactosamine; in heparan sulfate, it is either D-glucuronic acid or L-iduronic acid and N-acetyl-Dglucosamine; in keratan sulfate, it is D-galactose and N-acetyl-D-glucosamine.
Figure 19–36 examples of a small (decorin) and a large (aggrecan) proteoglycan found in the extracellular matrix. the figure compares these two proteoglycans with a typical secreted glycoprotein molecule, pancreatic ribonuclease B. all three are drawn to scale. the core proteins of both aggrecan and decorin contain oligosaccharide chains as well as the GaG chains, but these are not shown. aggrecan typically consists of about 100 chondroitin sulfate chains and about 30 keratan sulfate chains linked to a serine-rich core protein of almost 3000 amino acids. Decorin “decorates” the surface of collagen fibrils, hence its name.
RIBONUCLEASE (MW ~15,000) short, branched oligosaccharide side chain fibroblasts, syndecans can be found in cell–matrix adhesions, where they modulate integrin function by interacting with fibronectin on the cell surface and with cytoskeletal and signaling proteins inside the cell. As we discuss later, syndecan and other proteoglycans also interact with soluble peptide growth factors, influencing their effects on cell growth and proliferation.
Collagens are the Major proteins of the Extracellular Matrix
The collagens are a family of fibrous proteins found in all multicellular animals. They are secreted in large quantities by connective-tissue cells, and in smaller quantities by many other cell types. As a major component of skin and bone, collagens are the most abundant proteins in mammals, where they constitute 25% of the total protein mass.
The primary feature of a typical collagen molecule is its long, stiff, triple-stranded helical structure, in which three collagen polypeptide chains, called α chains, are wound around one another in a ropelike superhelix (Figure 19–39).
0.5 µm aggrecan aggregate
Figure 19–37 An aggrecan aggregate from fetal bovine cartilage. (a) an electron micrograph of an aggrecan aggregate shadowed with platinum. Many free aggrecan molecules are also visible.