Distinctive Expression Patterns of Heparan Sulfate O-Sulfotransferases and Regional Differences in Heparan Sulfate Structure in Chick Limb Buds*
Distinctive Expression Patterns of Heparan Sulfate O-Sulfotransferases and Regional Differences in Heparan Sulfate Structure in Chick Limb Buds*
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DOI：
10.1074/jbc.m307304200
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发表时间：
2004-02
影响因子：
4.8
通讯作者：
Ken Nogami;Hiroaki Suzuki;H. Habuchi;Naoki Ishiguro;H. Iwata;K. Kimata
中科院分区：
文献类型：
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作者：
Ken Nogami;Hiroaki Suzuki;H. Habuchi;Naoki Ishiguro;H. Iwata;K. Kimata
鸡肢芽中的骨骼组织发育和图案化已知是在各种肝素结合细胞生长因子如成纤维细胞生长因子和骨形态发生蛋白的时空控制下。蛋白聚糖硫酸乙酰肝素（HS）链上的不同结构区域可能与这些细胞生长因子结合能力的区域差异有关，通过这些细胞生长因子可以选择性地与靶细胞相互作用并调节其在这些过程中的信号传导。本研究首次通过cDNA克隆证实了鸡胚中存在一种硫酸乙酰肝素2-O-磺基转移酶（HS 2ST）和两种硫酸乙酰肝素6-O-磺基转移酶亚型（HS 6ST-1和-2），它们具有不同的底物特异性。接下来，我们通过整体原位杂交显示，HS 6ST-1和HS 6ST-2转录物分别优先定位于肢芽的前近端区域和后近端区域，而HS 2ST转录物在整个芽中分布相当均匀。从翅芽的不同区域的HS的结构分析表明，在6-O-硫酸残基是更丰富的近端比远端区域，而艾杜糖醛酸6-O-硫酸残基是丰富的前近端区域和葡萄糖醛酸6-O-硫酸残基在后近端区域的变化。这些结果表明，HS与不同的硫酸化模式创建多个磺基转移酶活动提供了一个适当的细胞外环境的形态发生信号转导。
The skeletal tissue development and patterning in chick limb buds are known to be under the spacio-temporal control of various heparin-binding cell growth factors such as fibroblast growth factors and bone morphogenetic proteins. Different structural regions on heparan sulfate (HS) chains of proteoglycans could be implicated in regional differences in the binding capacities of these cell growth factors, by which they could selectively interact with targeted cells and regulate their signaling in those processes. In this study we first demonstrated by cDNA cloning that one heparan sulfate 2-O-sulfotransferase (HS2ST) and two isoforms of heparan sulfate 6-O-sulfotransferase (HS6ST-1 and -2) occurred in chick embryos and had different substrate specificities each other. We next showed by whole mount in situ hybridization that the HS6ST-1 and HS6ST-2 transcripts were preferentially localized to the anterior proximal region and at the posterior proximal region of the limb bud, respectively, whereas the HS2ST transcript was distributed rather uniformly throughout the bud. Analyses of the structures of HS from different regions of the wing buds have shown variation in that 6-O-sulfated residues are more abundant in the proximal than distal region, whereas iduronosyl 6-O-sulfated residues are abundant in the anterior proximal region and glucuronosyl 6-O-sulfated residues in the posterior proximal region. These results suggest that HS with different sulfation patterns created with multiple sulfotransferase activities provides an appropriate extracellular environment for morphogenetic signal transduction.