Life without Perlecan Has Its Problems

Perlecan is a large heparan sulfate proteoglycan with a wide tissue distribution and multiple potential functions (see Iozzo 1998). The glycosaminoglycan chains, located in the NH₂-terminal domain of the core protein, bind basic FGF-2 and have been shown to promote the mitogenic and angiogenic activities of FGF-2. They also interact with the basement membrane components, laminin-1 and collagen IV, and are thought to represent a barrier to the passage of cationic macromolecules across glomerular basement membranes in the kidney. The 400–450-kD core protein, composed of several protein modules arranged in five distinct domains, binds to a variety of small and large molecules, including FGF-7, fibronectin, heparin, laminin-1, PDGF-BB, and integrins (Fig. 1). The physiological significance of such interactions is illustrated by the demonstration that lowering of perlecan levels by stable expression of antisense...