Another important function of hyaluronan is to immobilize certain molecules in the desired location of the ECM. For instance, ECM contains binding sites for several growth factors, such as TGF-. The binding of growth factors to proteoglycans may cause either their local aggregation or dispersion, which in turn either inhibits or enhances the movement of migrating macromolecules, microorganisms, or metastatic cancer cells in the extracellular environment. In addition, hyaluronan molecules act as efficient insulators,
TABLE Glycosaminoglycans6.3 Molecular Disaccharide Name Weight (kDa) Composition Localization Function Hyaluronan 100–10,000 D-Glucuronic acid Synovial fluid, vitreous Large polymers of N-acetylglucosamine humor, ECM of connective hyaluronan can displace tissues a large volume of water. Thus this polymer is excellent lubricant and shock absorber Chondroitin 25 D-Glucuronic acid 4-sulfate N-acetylgalactosamine Chondroitin sulfates and 4-sulfate hyaluronan are fundamental components of aggrecan found in articular cartilage. Aggrecan confers on articular cartilage shock-Chondroitin 25 D-Glucuronic acid absorbing properties 6-sulfate N-acetylgalactosamine 6-sulfate Dermatan 35 L-Iduronic acid Skin, blood vessels, Dermatan sulfate proteogly-sulfate N-acetylgalactosamine heart valves cans have been implicated 4-sulfate in cardiovascular disease, tumorigenesis, infection, wound repair, fibrosis, and as a modulator in cell behavior Keratan 10 Galactose or galactose Bone, cartilage, cornea Keratan sulfate proteoglycans sulfate 6-sulfate N-acetylgluco-function in cellular recognition samine 6-sulfate of protein ligands, axonal guidance, cell motility, corneal transparency, and embryo implantation Heparan 15 Glucuronic acid Basal lamina, normal Facilitates interactions with sulfate or L-iduronic acid component of cell fibroblastic growth factor 2-sulfate N-sulfamyl-surface (FGF) and its receptor glucosamine or N-acetyl-glucosamine Heparin 40 Glucuronic acid Limited to granules of Functions as an anticoagulant, or L-iduronic acid mast cells and facilitates interactions with 2-sulfate N-sulfamyl-basophiles FGF and its receptor glucosamine or N-acetylglucosamine 6-sulfate Cartilage, bone, heart valves kDa, kilodaltons.
because other macromolecules have difficulty diffusing through the dense hyaluronan network. With this property, hyaluronan (and other polysaccharides) regulates the distribution and transport of plasma proteins within the connective tissue.
Proteoglycans are composed of GAGs covalently attached to core proteins.
The majority of GAGs in the connective tissue are linked to core proteins, forming proteoglycans. The GAGs extend perpendicularly from the core in a brushlike structure. The linkage of GAGs to the protein core involves a specific trisaccharide composed of two galactose residues and a xylulose residue. The trisaccharide linker is coupled through an O-glycosidic bond to the protein core that is rich in serine and threonine residues, allowing multiple GAG attachments. Proteoglycans are remarkable for their diversity (Fig. 6.17). The number of GAGs attached to the protein core varies from 1 (i.e., decorin) to more than 200 (i.e., aggrecan). A core protein may have identical GAGs attached to it (as in the