Syndecan-4 and integrins: combinatorial signaling in cell adhesion

It is now becoming clear that additional transmembrane components can modif y integrin-mediated adhesion. Syndecan-4 is a transmembrane heparan sulfate proteoglycan whose external glycosaminoglycan chains can bind extracellula r matrix ligands and whose core protein cytoplasmic domain can signal durin g adhesion. Two papers in this issue of JCS demonstrate, through transfecti on studies, that syndecan-4 plays roles in the formation of focal adhesions and stress fibers. Overexpression of syndecan-4 increases focal adhesion f ormation, whereas a partially truncated core protein that lacks the binding site for protein kinase C alpha and phosphatidylinositol 4,5-bisphosphate acts as a dominant negative inhibitor of focal adhesion formation. Focal ad hesion induction does not require interaction between heparan sulfate glyco saminoglycan and ligand but can occur when non-glycanated core protein is o verexpressed; this suggests that oligomerization of syndecan-4 plays a majo r role in signaling from the extracellular matrix in adhesion.