N-SYNDECAN - STRUCTURE AND FUNCTION OF A TRANSMEMBRANE HEPARAN-SULFATE PROTEOGLYCAN

N-syndecan is a member of the syndecan family of transmembrane heparan sulfate proteoglycans that was cloned initially from neonatal rat Sch wann cells and is the principal syndecan expressed during early postna tal development in the central and peripheral nervous systems. Purifie d N-syndecan binds in vitro with high affinity to several extracellula r regulatory ligands, including basic fibroblast growth factor, the se creted adhesive protein heparin binding growth-associated molecule, an d a novel collagen-like protein secreted by Schwann cells. These extra cellular ligands utilize the heparan sulfate chains of N-syndecan for binding. Based on the striking amino acid sequence homology of the cyt oplasmic domain of N-syndecan to syndecan-1, it is proposed that N-syn decan associates with the actin-based cytoskeleton. N-syndecan core pr oteins self associate by means of an unusual dimerization motif compri sed of the transmembrane domain and a short flanking sequence in the e ctodomain. Similar to other single transmembrane domain receptor prote ins, it is suggested that ligand-regulated dimerization of N-syndecan represents a mechanism for regulating downstream signaling activities. In rat brain tissue a significant fraction of the N-syndecan molecule s are present in a soluble form, presumably as a result of proteolytic membrane shedding. A model is presented for morphoregulatory activity of N-syndecan in which extracellular ligand-induced clustering of N-s yndecan molecules on the cell surface promotes cytoskeletal associatio n and reorganization. Membrane shedding separates the functional domai ns of the proteoglycan and terminates this activity.