Protomer assembly begins when the three NC1 domains assemble to form an NC1 trimer (Fig. 5.30). The next step in the assembly of the basal lamina structure is the formation of type IV collagen dimer molecules. This is achieved when two NC1 trimers interact to form an NC1 hexamer. Next, four dimers join in the region of the 7S domain to form a tetramer. The 7S domain of the tetramer (called the 7S box) determines the geometry of the tetramer. Finally, the type IV collagen scaffold is formed when other collagen tetramers interact end to end with each other. This scaffold forms the suprastructure of the basal lamina. Assembly of this suprastructure is genetically determined. Those containing [1(IV)]22(IV) protomers are found in all basal laminae. Those containing 3(IV)4 (IV)5(IV) protomers occur mainly in the kidney and lungs, and those containing [5(IV)]26(IV) protomers are restricted to the skin, esophagus, and Bowman capsule in the kidney.
Basal lamina self-assembly is initiated by the polymerization of laminins on the basal cell domain and interaction with the type IV collagen suprastructure.
The constituents of the basal lamina come together in a process of self-assembly to form a sheetlike structure. This process is initiated by both type IV collagen and laminins. The primary sequence of these molecules contains information for their self-assembly (other molecules of the basal lamina are incapable of forming sheetlike structures by themselves). Studies using cell lines have shown that the first step in self-assembly of the basal lamina is calcium-dependent polymerization of laminin molecules on the basal cell surface domain (Fig. 5.31). This process is aided by CAMs (integrins). At the same time, the type IV collagen suprastructure becomes associated with laminin polymers. These two structures are joined together primarily by entactin/nidogen bridges and are additionally secured by other proteins (perlecan, agrin, fibronectin, and so forth). The scaffold of type IV collagen and laminins provides the site for other basal lamina molecules to interact and form the fully functional basal lamina.
FIGURE 5.30 • Formation of the type IV collagen suprastructure. Each type IV collagen molecule has three domains: an amino-terminus (7S domain), a middle collagenous helical domain, and a carboxy-terminus (NC1 domain). The NC1 domain initiates assembly of the type IV collagen protomer, which consists of three molecules. Protomer formation proceeds like a zipper from the NC1 domain toward the 7S domain, resulting in a fully assembled protomer. The next step in assembly is the dimerization of type IV collagen protomers. Two type IV collagen protomers become connected via their NC1 domains, and their two NC1 trimers join together to form an NC1 hexamer. Next, four dimers join together at their 7S domains to form tetramers connected by the 7S box. These tetramers interact to form the type IV collagen suprastructure via their interactions with the 7S domains of other tetramers and also by lateral associations between type IV collagen protomers.
A layer of reticular fibers underlies the basal lamina.