The alpha 5 beta 1 integrin fibronectin receptor, but not the alpha 5 cytoplasmic domain, functions in an early and essential step in fibronectin matrix assembly.
The alpha 5 beta 1 integrin fibronectin receptor, but not the alpha 5 cytoplasmic domain, functions in an early and essential step in fibronectin matrix assembly.
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发表时间：
1993-10
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通讯作者：
Chuanyue Wu;J. Bauer;R. Juliano;John A. McDonald
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作者：
Chuanyue Wu;J. Bauer;R. Juliano;John A. McDonald
α 5 β 1整联蛋白介导细胞在纤连蛋白上的粘附和迁移，纤连蛋白是一种对正常脊椎动物胚胎发育至关重要的糖蛋白。迄今为止报道的间接证据表明，该受体也在纤连蛋白基质的沉积中发挥作用。我们使用分子遗传学方法来严格评估α 5 β 1整合素的这种作用。α 5整合素表达缺陷的突变中国仓鼠卵巢（CHO）细胞不能组装纤连蛋白基质。通过用编码人α 5链的全长cDNA转染α 5 β 1整联蛋白来重建α 5 β 1整联蛋白表达，完全恢复了纤连蛋白基质组装。表达缺乏胞质结构域的α 5链的CHO细胞也组装纤连蛋白基质。去除α 5的胞质结构域似乎增加了其在纤连蛋白基质组装中的活性。除了α 5 β 1整联蛋白与纤连蛋白的含RGD结构域结合之外，细胞必须以高亲和力与纤连蛋白的氨基末端29-kDa基质组装结构域结合以形成纤连蛋白基质。对α 5缺陷型CHO细胞的研究表明，α 5 β 1整联蛋白的表达也是细胞结合纤连蛋白中含有该独特位点的片段所必需的，并且纤连蛋白基质增加了29-kDa片段的结合。因此，α 5 β 1整联蛋白不仅介导细胞与纤连蛋白的粘附，而且在纤连蛋白基质的组装中发挥重要作用。这种作用包括直接结合纤连蛋白和调节一个独特的结合事件，涉及纤连蛋白的氨基末端基质组装结构域与细胞表面的相互作用。
The alpha 5 beta 1 integrin mediates cell adhesion and migration on fibronectin, a glycoprotein critical for normal vertebrate embryonic development. Indirect evidence reported to date suggests that this receptor also functions in the deposition of fibronectin matrices. We used a molecular genetic approach to critically evaluate this role of alpha 5 beta 1 integrins. Mutant Chinese hamster ovary (CHO) cells deficient in alpha 5 integrin expression could not assemble a fibronectin matrix. Reconstituting alpha 5 beta 1 integrin expression by transfecting them with a full-length cDNA encoding the human alpha 5 chain completely restored fibronectin matrix assembly. CHO cells expressing an alpha 5 chain lacking the cytoplasmic domain also assembled a fibronectin matrix. Removing the cytoplasmic domain of alpha 5 appears to increase its activity in fibronectin matrix assembly. In addition to alpha 5 beta 1 integrin binding to fibronectin's RGD-containing domain, cells must bind with high affinity to fibronectin's amino-terminal 29-kDa matrix assembly domain to form a fibronectin matrix. Studies with the alpha 5-deficient CHO cells show that the expression of alpha 5 beta 1 integrin is also necessary for cells to bind fragments containing this distinct site in fibronectin and that a fibronectin matrix increases binding of the 29-kDa fragment. Thus, alpha 5 beta 1 integrins not only mediate cell adhesion to fibronectin, but also play an essential role in the assembly of a fibronectin matrix. This role includes direct binding to fibronectin and modulating a distinct binding event involving the interaction of fibronectin's amino-terminal matrix assembly domain with the cell surface.