Extracellular regulation of developmental cell signaling by XtSulf1

Extracellular regulation of developmental cell signaling by XtSulf1
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DOI:
10.1016/j.ydbio.2008.05.554
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发表时间:
2008-08-15
影响因子:
2.7
通讯作者:
Pownall, Mary E.
Pownall, Mary E.
中科院分区:
生物学3区
文献类型:
--
作者:
Freeman, Stephen D.;Moore, Wendy M.;Pownall, Mary E.

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硫酸乙酰肝素蛋白聚糖(HSPG)在呈递到细胞表面之前在高尔基体中合成和修饰。修饰包括在沿着硫酸乙酰肝素(HS)链的糖残基上的特定位置添加硫酸酯基团,这导致结构异质性,其支持HSPG以高亲和力结合许多不同蛋白质(包括生长因子及其受体)的能力。Sulf 1编码存在于细胞外并具有活性的6-0-endosulfatase,提供了通过HS的合成后重塑产生结构多样性的进一步机制。在这里,我们使用非洲爪蟾胚胎,以证明在体内,Xtsulf 1在调节细胞信号在发展过程中起着重要的作用。我们表明,虽然XtSulf 1可以增强Wnt 11的轴诱导活性,但XtSulf 1在胚胎发生过程中起作用,限制BMP和FGF信号传导,(C)2008 Elsevier Inc. All rights reserved.
Heparan Sulfate proteoglycans (HSPGs) are synthesised and modified in the Golgi before they are presented at the cell surface. Modifications include the addition of sulfate groups at specific positions on sugar residues along the heparan sulfate (HS) chain which results in a structural heterogeneity that underpins the ability of HSPGs to bind with high affinity to many different proteins, including growth factors and their receptors. Sulf1 codes for a 6-0-endosulfatase that is present and active extracellularly, providing a further mechanism to generate structural diversity through the post-synthetic remodelling of HS. Here we use Xenopus embryos to demonstrate in vivo that Xtsulf1 plays an important role in modulating cell signaling during development. We show that while XtSulf1 can enhance the axis-inducing activity of Wnt11, XtSulf1 acts during embryogenesis to restrict BMP and FGF signaling, (C) 2008 Elsevier Inc. All rights reserved.