Syndecan-2 induces filopodia by active cdc42Hs

The syndecans, a family of transmembrane heparan sulfate proteoglycans, are ubiquitous molecules whose intracellular function is still unknown. To exa mine the function of syndecan-2, one of the most abundant heparan sulfate p roteoglycan in fibroblasts, we performed transfection studies in COS-1 and Swiss 3T3 cells. Endogenous syndecan-2 colocalized with F-actin in cortical structures. Overexpression of full-length syndecan-2 induced the formation of long filopodia-like structures, These changes correlated with a rearran gement of the actin cytoskeleton, which strongly colocalized with syndecan- 2. Overexpression of syndecan-2 lacking the extracellular domain increased the number of microspikes on the cell surface but failed to induce filopodi a. Addition of heparin blocked the effect of full-length syndecan-2, sugges ting that heparan sulfate chains in the extracellular domain are necessary to induce filopodia. Coexpression of cdc42Hs negative-dominant N17 blocked syndecan-2-induced filopodia and cdc42Hs positive-dominant V12 had a synerg ic effect. This indicates that active cdc42Hs is necessary for syndecan-2 i nduction of filopodia. These results provide a link. between syndecan-2, ac tin cytoskeleton, and cdc42Hs. (C) 1999 Academic Press.