N-syndecan (syndecan 3) from neonatal rat brain binds basic fibroblast growth factor.
The cell surface proteoglycan N-syndecan (syndecan 3) was isolated from neonatal rat brain. Purified brain N-syndecan had biochemical properties very similar to N-syndecan previously identified in Schwann cells: it contained mainly, if not exclusively, heparan sulfate glycosaminoglycan chains and had a core protein with an apparent molecular mass of 120 kDa by sodium dodecyl sulfate-gel electrophoresis. We examined the interactions between purified N-syndecan and extracellular ligands using a solid phase binding assay. It was found that among all proteins tested, including a variety growth factors and extracellular matrix molecules, only basic fibroblast growth factor (bFGF) exhibited significant N-syndecan binding. N-syndecan binding to bFGF was saturable and exhibited a KD = 0.5 nM. Soluble bFGF effectively competed with immobilized bFGF for binding to N-syndecan, indicating that these two proteins also interact in solution. Heparin and heparan sulfate, but not chondroitin sulfate, inhibited N-syndecan-bFGF binding. Isolated N-syndecan core protein did not exhibit significant binding to bFGF. Thus, the heparan sulfate chains of N-syndecan, rather than its core protein, appear to be responsible for binding to bFGF. Interestingly, acidic fibroblast growth factor, which is structurally similar to bFGF, did not exhibit significant N-syndecan binding. N-syndecan also did not bind to several other heparin-binding proteins used in this study, indicating a high degree of specificity for the N-syndecan-bFGF interaction. Both N-syndecan and bFGF are abundant in neonatal brain, suggesting that N-syndecan may function as a co-receptor for bFGF during nerve tissue development.
Chernousov
M A
MA
Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822.
Carey
D J
DJ
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D012995:Solubility; D053670:Syndecan-3
D008562:Membrane Glycoproteins; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; C508301:SDC3 protein, human; C508302:Sdc3 protein, mouse; C508303:Sdc3 protein, rat; D053670:Syndecan-3; D016222:Fibroblast Growth Factor 2