 Laminins. These cross-shaped glycoprotein molecules (140 to 400 kilodaltons) are composed of three polypeptide chains. They are essential in initiating the assembly of the basal lamina. Laminins possess binding sites for different integrin receptors in the basal domain of the overlying epithelial cells. They are involved in many cellto–extracellular matrix interactions. They also play roles in the development, differentiation, and remodeling of epithelium. There are approximately 15 different variations of laminin molecules.
 Entactin/nidogen. This small, rodlike sulfated glycoprotein (150 kilodaltons) serves as a link between laminin and the type IV collagen network in almost all basal laminae. Each entactin molecule is organized into distinct domains that bind calcium, support cell adhesion, promote neu
FIGURE 5.29 • Electron micrograph of epithelial cells preserved by low-temperature, high-pressure freezing. This electron micrograph shows basal domain of an epithelial cell obtained from human skin. The specimen was prepared by low-temperature, high-pressure freezing, which retains more tissue components than does chemical fixation. Note that a separate lamina densa or lamina lucida is not seen in this preparation. The lamina lucida is most likely an artifact that appears as the epithelial cell shrinks away from a high concentration of macromolecules just basal of the epithelial cell. This region of highly concentrated macromolecules precipitates into the artifact known as the lamina densa. BL, basal lamina; HD, hemidesmosome; CF, collagen fibrils. 55,000. (Courtesy of Douglas R. Keene.) trophil chemotaxis and phagocytosis, and interact with laminin, perlecan, fibronectin, and type IV collagen.
 Proteoglycans. Most of the volume of the basal lamina is probably attributable to its proteoglycan content. Proteoglycans consist of a protein core to which heparan sulfate (e.g., perlecan, agrin), chondroitin sulfate (e.g., bamacan), or dermatan sulfate side chains are attached. Because of their highly anionic character, these molecules are extensively hydrated. They also carry a high negative charge; this quality suggests that proteoglycans play a role in regulating the passage of ions across the basal lamina. The most common heparan sulfate proteoglycan found in all basal laminae is the large multidomain proteoglycan perlecan (400 kilodaltons). It provides additional cross-links to the basal lamina by binding to laminin, type IV collagen, and entactin/nidogen. Agrin (500 kilodaltons) is another important molecule found almost exclusively in the glomerular basement membrane of the kidney. It plays a major role in renal filtration as well as in cell-to–extracellular matrix interactions.
The molecular structure of type IV collagen determines its role in the formation of the basal lamina network suprastructure.
The type IV collagen molecule is similar to other collagens in that it contains three polypeptide chains. Each chain has a short amino-terminus domain (7S domain), a long middle collagenous helical domain (which interacts with the remaining two chains in the fully assembled molecule), and a carboxy-terminus globular noncollagenous domain (NC1 domain). The six known chains of type IV collagen molecules (1 to 6) form three sets of triple helical molecules known as collagen protomers. They are designated as [1(IV)]22(IV); 3(IV)4(IV)5(IV), and [5(IV)]26(IV) protomers (see Table 6.2).