Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions
Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions
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DOI：
10.1074/jbc.275.8.5249
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发表时间：
2000-02-25
影响因子：
4.8
通讯作者：
Muramatsu, T
中科院分区：
文献类型：
--
作者：
Ishiguro, K;Kadomatsu, K;Muramatsu, T
纤连蛋白的两个结构域传递两种不同但协同的粘着斑形成所需的信号。来自细胞结合结构域的信号由整联蛋白介导，而来自肝素结合结构域的信号由硫酸乙酰肝素蛋白聚糖识别，其中多配体蛋白聚糖-4已被假设参与粘着斑形成。我们产生了syndecan-4缺陷的小鼠，以直接研究其作用。即使在成纤维细胞从syndecan-4缺陷小鼠，局灶性粘连形成，和肌动蛋白纤维通常终止于局灶性粘连时，他们培养的盖玻片上包被纤连蛋白或其细胞结合和肝素结合片段的混合物。然而，当在细胞结合片段上培养细胞并将肝素结合片段加入培养基中时，与野生型细胞相比，syndecan-4无效成纤维细胞中的粘着斑形成受损。因此，只有当纤连蛋白的肝素结合结构域的信号作为可溶形式递送时，最有可能从顶端表面递送时，多配体蛋白聚糖-4才是促进粘着斑形成所必需的。当信号作为基质结合形式递送时，其他分子也参与信号接收。
Two domains of fibronectin deliver two different but cooperative signals required for focal adhesion formation. The signal from the cell-binding domain is mediated by integrins, whereas the signal from the heparin-binding domain is recognized by heparan sulfate proteoglycans, of which syndecan-4 has been hypothesized to be involved in focal adhesion formation. We generated mice deficient in syndecan-4 to study its role directly. Even in fibroblasts from syndecan-4-deficient mice, focal adhesions were formed, and actin fibers terminated normally at focal adhesions when they were cultured on coverslips coated with fibronectin or with a mixture of its cell-binding and heparin-binding fragments. However, when the cells were cultured on the cell-binding fragment and the heparin-binding fragment was added to the medium, focal adhesion formation was impaired in the syndecan-4 null fibroblasts as compared with that in wild-type cells. Therefore, syndecan-4 is essential for promoting focal adhesion formation only when the signal of the heparin-binding domain of fibronectin is delivered as a soluble form, most probably from the apical surface, When the signal is delivered as a substratum-bound form, other molecule(s) also participate(s) in the signal reception.