Laminin is the primary organizer of the sheet structure, and, early in development, basal laminae consist mainly of laminin molecules. Laminins comprise a large family of proteins, each composed of three long polypeptide chains (α, β, and γ) held together by disulfide bonds and arranged in the shape of an asymmetric bouquet, like a bunch of three flowers whose stems are twisted together at the foot but whose heads remain separate (Figure 19–52). These heterotrimers can self-assemble in vitro into a network, largely through interactions between their heads, although interaction with cells is needed to organize the network into an orderly sheet. Since there are several isoforms of each type of chain, and these can associate in different combinations, many different laminins can be produced, creating basal laminae with distinctive properties. The laminin γ1 chain is, however, a component of most laminin heterotrimers; mice lacking it die during embryogenesis because they are unable to make basal laminae.
Type IV collagen is a second essential component of mature basal laminae, and it, too, exists in several isoforms. Like the fibrillar collagens that constitute the bulk of the protein in connective tissues such as bone or tendon, type IV collagen molecules consist of three separately synthesized long protein chains that twist together to form a ropelike superhelix; however, they differ from the fibrillar collagens in that the triple-stranded helical structure is interrupted in more than 20 regions, allowing multiple bends. Type IV collagen molecules interact via their terminal domains to assemble extracellularly into a flexible, feltlike network that gives the basal lamina tensile strength.
Laminin and type IV collagen interact with other basal lamina components, such as the glycoprotein nidogen and the proteoglycan perlecan, resulting in a highly cross-linked network of proteins and proteoglycans (Figure 19–53). The laminin molecules that generate the initial sheet structure first join to each other while bound to receptors on the surface of the cells that produce laminin. The cell-surface receptors are primarily members of the integrin family, but another important type of laminin receptor is dystroglycan, a proteoglycan with a core protein that spans the cell membrane, dangling its GAG chains in the extracellular space. Together, these receptors organize basal lamina assembly: they hold the laminin molecules by their feet, leaving the laminin heads positioned to interact so as to form a two-dimensional network. This laminin network then coordinates the assembly of the other basal lamina components.
In the kidney glomerulus, an unusually thick basal lamina acts as one of the layers of a molecular filter, helping to prevent the passage of macromolecules from the blood into the urine as urine is formed (see Figure 19–50). The proteoglycan in
Figure 19–52 The structure of laminin.