Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development
Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development
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DOI：
10.1074/jbc.273.8.4350
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发表时间：
1998-02-20
影响因子：
4.8
通讯作者：
Turnbull, JE
中科院分区：
文献类型：
--
作者：
Brickman, YG;Ford, MD;Turnbull, JE
硫酸乙酰肝素（HS）糖胺聚糖是成纤维细胞生长因子（FGF）活性的必需调节剂，并且似乎通过将特定形式的FGF偶联至适当的FGF受体而起作用。在神经发育期间，一种特定的HS蛋白聚糖能够快速地将其增强活性从FGF-2（当神经前体细胞增殖发生时）转换为FGF-1（当神经元分化发生时）。包括化学和酶促裂解、低压色谱和强阴离子交换高效液相色谱，我们分析了在这些关键发育阶段表达的不同HS。来自更成熟的胚胎脑的HS的6-O-硫酸化模式、总链长度和硫酸化结构域的数目有明显的改变，这些变化与HS增强FGF-1在触发以下事件中的作用的能力的转换相关：细胞分化由此看来，每个HS库被设计成在调节与特异性生长因子及其同源受体的复杂相互作用中起作用，并提示严格调节特异性，这些数据可用于构建HS链结构中受控变化的简单模型，其在神经元成熟的关键阶段具有功能性后果。
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.