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

Tarja Kinnunen, Erkki Raulo, Riitta Nolo, Marco Maccarana, Ulf Lindahl, Heikki Rauvala

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2243
Pages (from-to)2243-2248
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number4
DOIs
Publication statusPublished - 26 Jan 1996
Externally publishedYes

Fingerprint

Syndecan-3
Heparitin Sulfate
Neurons
Brain
Syndecans
Iduronic Acid
Heparin
heparitinsulfate lyase
Sulfates
Rats
pleiotrophin
Neuronal Outgrowth
Monosaccharides
Disaccharides
Extracellular Matrix Proteins
Laminin
Glycosaminoglycans
Glucosamine
Polysaccharides
Axons

Cite this

@article{339d4bd216d1459db5eaae8d15e25ff1,
title = "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",
abstract = "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.",
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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. / Kinnunen, Tarja; Raulo, Erkki; Nolo, Riitta; Maccarana, Marco; Lindahl, Ulf; Rauvala, Heikki.

In: Journal of Biological Chemistry, Vol. 271, No. 4, 2243, 26.01.1996, p. 2243-2248.

Research output: Contribution to journalArticle

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

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