SYNDECAN-1 MEDIATES CELL SPREADING IN TRANSFECTED HUMAN LYMPHOBLASTOID (RAJI) CELLS

Syndecan-1 is a cell surface proteoglycan containing a highly conserve d transmembrane and cytoplasmic domain, and an extracellular domain be aring heparan sulfate glycosaminoglycans. Through these domains, synde can-1 is proposed to have roles in growth factor action, extracellular matrix adhesion, and cytoskeletal organization that controls cell mor phology. To study the role of syndecan-1 in cell adhesion and cytoskel eton reorganization, mouse syndecan-1 cDNA was transfected. into human Raji cells, a lymphoblastoid cell line that grows as suspended cells and exhibits little or no endogenous cell surface heparan sulfate. Hig h expressing transfectants (Raji-S1 cells) bind to and spread on immob ilized thrombospondin or fibronectin, which are ligands for the hepara n sulfate chains of the proteoglycan. This binding and spreading is no t dependent on the cytoplasmic domain of the core protein, as mutants expressing core proteins with cytoplasmic deletions maintain the abili ty to spread, The spreading is mediated through engagement of the synd ecan-1 core protein, as the Raji-S1 cells also bind to and spread on i mmobilized mAb 281.2, an antibody specific for the ectodomain of the s yndecan-1 core protein. Spreading on the antibody is independent of th e heparan sulfate glycosaminoglycan chains and can be inhibited by com petition with soluble mAb 281.2, The spreading can be inhibited by tre atment with cytochalasin D or colchicine. These data suggest that the core protein of syndecan-1 mediates spreading through the formation of a multimolecular signaling complex at the cell surface that signals c ytoskeleton reorganization. This complex may form via intramembrane or extracellular interactions with the syndecan core protein.