Key Concepts of Section 20.4

• Connective tissue, such as tendon and cartilage, differs from other solid tissues in that most of its volume is made up of extracellular matrix (ECM) rather than cells.

• The synthesis of fibrillar collagen (e.g., types I, II, and III) begins inside the cell with the chemical modification of newly made α chains and their assembly into triple-helical procollagen within the endoplasmic reticulum. After secretion, procollagen molecules are cleaved, associate laterally, and are covalently cross-linked into bundles called fibrils, which can form larger assemblies called fibers (see Figure 20-27).

• The various collagens are distinguished by the ability of their helical and nonhelical regions to associate into fibrils, to form sheets, or to cross-link other collagen types (see Table 20-5).

• Proteoglycans consist of membrane-associated or secreted core proteins covalently linked to one or more glycosaminoglycan (GAG) chains, which are linear polymers of disaccharides that are often modified by sulfation.

• Cell-surface proteoglycans such as the syndecans facilitate cell-ECM interactions and help present certain external signaling molecules to their cell-surface receptors.

• Hyaluronan, a highly hydrated GAG, is a major component of the ECM of migrating and proliferating cells. Certain adhesion receptors bind hyaluronan to cells.

• Large proteoglycan aggregates containing a central hyaluronan molecule noncovalently bound to the core proteins of proteoglycan molecules (e.g., aggrecan) contribute to the ability of the matrix to resist compression forces (see Figure 20-32).

• Fibronectins are abundant multi-adhesive matrix proteins that play a key role in migration and cellular differentiation. They contain binding sites for integrins and ECM components (collagens, proteoglycans) and thus can attach cells to the ECM (see Figure 20-33).

• The tripeptide RGD motif Arg-Gly-Asp, found in fibronectins and some other matrix proteins, is recognized by several integrins.

• Elastic fibers permit repeated stretching and recoiling of tissues because of their highly elastic core of cross-linked, amorphous elastin, which is surrounded by a network of microfibrils that help assemble the fibers and regulate signaling mediated by TGF-β.

• The remodeling or degradation of ECM is mediated by a large number of secreted and cell-membrane-associated zinc metalloproteases that fall into several families (MMPs, ADAMs, ADAMTSs) and whose activities are regulated by protein inhibitors (TIMPs and RECK).