Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development.

2.50
Hdl Handle:
http://hdl.handle.net/10541/93027
Title:
Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development.
Authors:
Brickman, Y G; Ford, M D; Gallagher, John T; Nurcombe, V; Bartlett, P F; Turnbull, Jeremy E
Abstract:
Heparan sulfate (HS) glycosaminoglycans are essential modulators of fibroblast growth factor (FGF) activity and appear to act by coupling particular forms of FGF to appropriate FGF receptors. During neural development, one particular HS proteoglycan is able to rapidly switch its potentiating activity from FGF-2, as neural precursor cell proliferation occurs, to FGF-1, as neuronal differentiation occurs. Using various analytical techniques, including chemical and enzymatic cleavage, low pressure chromatography, and strong anion-exchange high performance liquid chromatography, we have analyzed the different HSs expressed during these crucial developmental stages. There are distinct alterations in patterns of 6-O-sulfation, total chain length, and the number of sulfated domains of the HS from the more mature embryonic brain. These changes correlate with a switch in the ability of the HS to potentiate the actions of FGF-1 in triggering cell differentiation. It thus appears that each HS pool is designed to function in the modulation of an intricate interaction with a specific growth factor and its cognate receptor, and suggests tightly regulated expression of specific, bioactive disaccharide sequences. The data can be used to construct a simple model of controlled variations in HS chain structure which have functional consequences at a crucial stage of neuronal maturation.
Affiliation:
Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia 3052.
Citation:
Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development. 1998, 273 (8):4350-9 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
20-Feb-1998
URI:
http://hdl.handle.net/10541/93027
PubMed ID:
9468484
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBrickman, Y Gen
dc.contributor.authorFord, M Den
dc.contributor.authorGallagher, John Ten
dc.contributor.authorNurcombe, Ven
dc.contributor.authorBartlett, P Fen
dc.contributor.authorTurnbull, Jeremy Een
dc.date.accessioned2010-02-25T11:47:15Z-
dc.date.available2010-02-25T11:47:15Z-
dc.date.issued1998-02-20-
dc.identifier.citationStructural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development. 1998, 273 (8):4350-9 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid9468484-
dc.identifier.urihttp://hdl.handle.net/10541/93027-
dc.description.abstractHeparan sulfate (HS) glycosaminoglycans are essential modulators of fibroblast growth factor (FGF) activity and appear to act by coupling particular forms of FGF to appropriate FGF receptors. During neural development, one particular HS proteoglycan is able to rapidly switch its potentiating activity from FGF-2, as neural precursor cell proliferation occurs, to FGF-1, as neuronal differentiation occurs. Using various analytical techniques, including chemical and enzymatic cleavage, low pressure chromatography, and strong anion-exchange high performance liquid chromatography, we have analyzed the different HSs expressed during these crucial developmental stages. There are distinct alterations in patterns of 6-O-sulfation, total chain length, and the number of sulfated domains of the HS from the more mature embryonic brain. These changes correlate with a switch in the ability of the HS to potentiate the actions of FGF-1 in triggering cell differentiation. It thus appears that each HS pool is designed to function in the modulation of an intricate interaction with a specific growth factor and its cognate receptor, and suggests tightly regulated expression of specific, bioactive disaccharide sequences. The data can be used to construct a simple model of controlled variations in HS chain structure which have functional consequences at a crucial stage of neuronal maturation.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCells, Cultured-
dc.subject.meshChromatography, Gel-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshFibroblast Growth Factors-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshHydrogen-Ion Concentration-
dc.subject.meshMice-
dc.subject.meshModels, Chemical-
dc.subject.meshMolecular Structure-
dc.subject.meshNitrous Acid-
dc.subject.meshOligosaccharides-
dc.titleStructural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development.en
dc.typeArticleen
dc.contributor.departmentDepartment of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia 3052.en
dc.identifier.journalThe Journal of Biological Chemistryen

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