Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). It is thought that syndecans often act in concert with other receptors. Alpha2beta1 and alpha6beta4 integrins cooperate with syndecan-1 (SDC1) during adhesion to laminins (laminin alpha-1 Hozumi et al. 2006, laminin gamma-2, Ogawa et al. 2007, Wang et al. 2010). Interaction betweey SDC1 and alpha2beta1 integrin regulates cell adhesion to collagen (Vuoriluoto et al. 2008). SDC1 associates directly with the alphaVBeta3 and alphaVBeta5 integrins via its extracellular domain (Beauvais et al. 2004, McQuade et al. 2006). This association is required for integrin activation in a variety of carcinomas and probably reflects a generic role for the syndecan family as signaling 'hubs' at ECM adhesion sites (Fig. 1, Rapraeger 2013).
The relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.