PROTEIN-KINASE-C REGULATES THE RECRUITMENT OF SYNDECAN-4 INTO FOCAL CONTACTS

Cell surface heparan sulfate proteoglycans have been implicated as co- receptors facilitating cell adhesion and growth factor binding. Recent studies on the role of a family of transmembrane heparan sulfate prot eoglycans, syndecans, in cell adhesion has identified one member, synd ecan-4, to be present within focal contacts. The current study investi gates the mechanisms regulating the association of syndecan-4 with foc al contacts based upon its immunolocalization with vinculin in quiesce nt, serum-stimulated, and 12-O-tetradecanoylphorbol 13-acetate (TPA)-i nduced cultures. In quiescent cells, syndecan-4 did not localize to fo cal contacts. However, activation of protein kinase C by TPA or serum induces the active recruitment of syndecan-4 into focal contacts. This induction preferentially localizes syndecan-4 to focal contacts behin d the leading lamella, the subnuclear region, and along the trailing e dge of migratory cells. Focal contacts in either freshly adhered cells or in the leading lamellae of migrating cells did not stain for synde can-4. In addition to the observed subcellular distribution and recrui tment, syndecan-4 was observed to co-localize with endogenously synthe sized fibronectin fibrils within focal contacts as well as with fibril s present in the matrix. These findings suggest that protein kinase C activation results in syndecan-4 recruitment to focal contacts and its association with sites of matrix deposition.