Figure 19–53 A model of the molecular structure of a basal lamina. (a) the basal lamina is formed by specific interactions (B) between the proteins laminin, type IV collagen, and nidogen, and the proteoglycan perlecan. Arrows in (B) connect molecules that can bind directly to each other. there are various isoforms of type IV collagen and laminin, each with a distinctive tissue distribution. transmembrane laminin receptors  (integrins and dystroglycan) in the  plasma membrane are thought to  organize the assembly of the basal lamina; only the integrins are shown. (Based on h. Colognato and p.D. Yurchenco, Dev. Dyn. 218:213–234, 2000. With permission from Wiley-Liss.) shell of REGENERATED residual returns to site of original junction nerve cut new acetylcholine receptors become concentrated at site of originalDEGENERATED MUSCLE AND NERVE REGENERATED junctionMUSCLE FIBER with special isoforms of type IV collagen and laminin and a proteoglycan called agrin. After a nerve or muscle injury, the basal lamina at the synapse has a central role in reconstructing the synapse at the correct location (Figure 19–54). Defects in components of the basal lamina at the synapse are responsible for some forms of muscular dystrophy, in which muscles develop normally but then degenerate later in life.
Cells have to Be able to Degrade Matrix, as Well as Make It
The ability of cells to degrade and destroy extracellular matrix is as important as their ability to make it and bind to it. Rapid matrix degradation is required in processes such as tissue repair, and even in the seemingly static extracellular matrix of adult animals there is a slow, continuous turnover, with matrix macromolecules being degraded and resynthesized. This allows bone, for example, to be remodeled so as to adapt to changes in the stresses on it.
From the point of view of individual cells, the ability to cut through matrix is crucial in two ways: it enables them to divide while embedded in matrix, and it enables them to travel through it. Cells in connective tissues generally need to be able to stretch out in order to divide. If a cell lacks the enzymes needed to degrade the surrounding matrix, it is strongly inhibited from dividing, as well as being hindered from migrating.
Localized degradation of matrix components is also required wherever cells have to escape from confinement by a basal lamina. It is needed during normal branching growth of epithelial structures such as glands, for example, to allow the population of epithelial cells to increase, and needed also when white blood cells migrate across the basal lamina of a blood vessel into tissues in response to infection or injury. Matrix degradation is important both for the spread of cancer cells through the body and for their ability to proliferate in the tissues that they invade (discussed in Chapter 20).
In general, matrix components are degraded by extracellular proteolytic enzymes (proteases) that act close to the cells that produce them. Many of these proteases belong to one of two general classes. The largest group, with about 50 members in vertebrates, is the matrix metalloproteases, which depend on bound Ca2+ or Zn2+ for activity. The second group is the serine proteases, which have a highly reactive serine in their active site. Together, metalloproteases and serine