Proteoglycans consist of negatively charged sulfated unbranched glycosaminoglycan (GAG) chains that are covalently attached to transmembrane- or membrane-anchored proteins. Such proteins carrying various GAG chains are referred to as core proteins. GAGs consist of a repeating disaccharide unit. The major GAGs are hyaluronic acid, dermatan sulfate, chondroitin sulfate (CS), heparan sulfate (HS), and keratin sulfate. Different GAG moieties are found on different core proteins, including syndecans, glypicans, betaglycan, lumican, and perlecan. This chapter discusses the syndecan family of core proteins.

Syndecans are a family of transmembrane proteins that perform several distinct functions (Table 44–1). By virtue of their wide expression and their ability to interact with a large number of ligands, ranging from circulating growth factors to extracellular matrix (ECM) proteins, syndecans can integrate and coordinate various cellular signaling inputs. Furthermore, they can activate specific signaling cascades and induce profound changes in cell structure and behavior. This ability to integrate and modulate various signaling inputs, as well as to signal in their own right, has earned this family of cell surface receptors the name “tuners of transmembrane signaling” (1).

In addition, due to shedding of their extracellular domains that include large HS and CS chains, syndecans have the ability to alter the protein and water context of the surrounding ECM, greatly affecting storage, distribution, and transport of many extracellular proteins.

SYNDECAN STRUCTURE

The syndecan family in all vertebrates is composed of four genes (syndecan-1, -2, -3, -4). Each syndecan possesses a protein core which, in its extracellular domain, has attachment sites for three to five HS and/or CS chains (Figure 44.1).