TY - JOUR
T1 - Neurite Outgrowth in Brain Neurons Induced by Heparin-binding Growth-associated Molecule (HB-GAM) Depends on the Specific Interaction of HB-GAM with Heparan Sulfate at the Cell Surface
AU - Kinnunen, Tarja
AU - Raulo, Erkki
AU - Nolo, Riitta
AU - Maccarana, Marco
AU - Lindahl, Ulf
AU - Rauvala, Heikki
PY - 1996/1/26
Y1 - 1996/1/26
N2 - Heparin-binding growth-associated molecule (HB-GAM) is a cell surface- and extracellular matrix-associated protein that lines developing axon-s in vivo and promotes neurite outgrowth in vitro. Because JV-syndecan (syndecan-3) was found to function as a receptor in HB-GAM-induced neurite outgrowth, we have now studied whether the heparan sulfate side chains of Nsyndecan play a role in HB-GAM-neuron interactions. JV-Syndecan from postnatal rat brain was found to inhibit HB-GAM-induced but not laminin-induced neurite outgrowth when added to the assay media. The inhibitory activity was abolished by treating JV-syndecan with heparitinase, but it was retained in N-syndecan-derived free glycosaminoglycan chains, suggesting that N-syndecan heparan sulfate at the cell surface is involved in HB-GAM-induced neurite outgrowth. Binding to HB-GAM and inhibition of neurite outgrowth was observed with heparin-related polysaccharides only; galactosaminoglycans were inactive. Significant inhibition of neurite outgrowth was induced by heparin and by N-syndecan heparan sulfate but not by heparan sulfates from other sources. A minimum of 10 monosaccharide residues were required for HB-GAM binding, as well as for inhibition of HB-GAM-induced neurite outgrowth. Experiments with selectively desulfated heparins indicated that 2-O-sulfated iduronic acid units, in particular, are of importance to the interaction with HB-GAM, whereas glucosamine JV-sulfate and 6-O-sulfate groups were implicated to a lesser extent. Structural analysis of JV-syndecan from 6-day-old rat brain indicated that the heparan sulfate chains contain sequences of contiguous, N-sulfated disaccharide units with an unusually high proportion (82%) of 2-O-sulfated iduronic acid residues. We suggest that this property of N-syndecan heparan sulfate is essential for HJB-GAM binding and induction of neurite outgrowth.
AB - Heparin-binding growth-associated molecule (HB-GAM) is a cell surface- and extracellular matrix-associated protein that lines developing axon-s in vivo and promotes neurite outgrowth in vitro. Because JV-syndecan (syndecan-3) was found to function as a receptor in HB-GAM-induced neurite outgrowth, we have now studied whether the heparan sulfate side chains of Nsyndecan play a role in HB-GAM-neuron interactions. JV-Syndecan from postnatal rat brain was found to inhibit HB-GAM-induced but not laminin-induced neurite outgrowth when added to the assay media. The inhibitory activity was abolished by treating JV-syndecan with heparitinase, but it was retained in N-syndecan-derived free glycosaminoglycan chains, suggesting that N-syndecan heparan sulfate at the cell surface is involved in HB-GAM-induced neurite outgrowth. Binding to HB-GAM and inhibition of neurite outgrowth was observed with heparin-related polysaccharides only; galactosaminoglycans were inactive. Significant inhibition of neurite outgrowth was induced by heparin and by N-syndecan heparan sulfate but not by heparan sulfates from other sources. A minimum of 10 monosaccharide residues were required for HB-GAM binding, as well as for inhibition of HB-GAM-induced neurite outgrowth. Experiments with selectively desulfated heparins indicated that 2-O-sulfated iduronic acid units, in particular, are of importance to the interaction with HB-GAM, whereas glucosamine JV-sulfate and 6-O-sulfate groups were implicated to a lesser extent. Structural analysis of JV-syndecan from 6-day-old rat brain indicated that the heparan sulfate chains contain sequences of contiguous, N-sulfated disaccharide units with an unusually high proportion (82%) of 2-O-sulfated iduronic acid residues. We suggest that this property of N-syndecan heparan sulfate is essential for HJB-GAM binding and induction of neurite outgrowth.
KW - Receptor-Like Protein Tyrosine Phosphatases, Class 5
KW - neoplasms
KW - Heparin-binding growth
UR - http://www.scopus.com/inward/record.url?scp=0030050980&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.4.2243
DO - 10.1074/jbc.271.4.2243
M3 - Article
C2 - 8567685
AN - SCOPUS:0030050980
VL - 271
SP - 2243
EP - 2248
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 4
M1 - 2243
ER -