Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by α5β1 and αvβ3 integrins
Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by α5β1 and αvβ3 integrins
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DOI：
10.1074/jbc.m303159200
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发表时间：
2003-09-05
影响因子：
4.8
通讯作者：
Kielty, CM
中科院分区：
文献类型：
--
作者：
Bax, DV;Bernard, SE;Kielty, CM
原纤蛋白是微纤维的主要糖蛋白组分，其在弹性原纤维形成期间形成原弹性蛋白的模板。我们已经研究了细胞粘附组装纯化微纤维，其分子基础。人皮肤成纤维细胞表现出Arg-Gly-Asp和阳离子依赖性粘附微纤维和重组的Escherichin-1蛋白片段。整合素α（5）β（1）与β-内酰胺酶配体的强相互作用被鉴定出来，但整合素α（v）β（3）也有助于细胞粘附。荧光激活细胞分选分析证实了这些细胞上存在丰富的α（5）β（1）和一些α（v）β（3）受体。粘附微纤维和Arg-Gly-Asp-containing pepsin-1蛋白片段诱导信号传导事件，导致细胞铺展，改变细胞骨架组织，并增强细胞外pepsin-1沉积。当接种在白蛋白或纤连蛋白上时，细胞形状的差异意味着底物特异性α（5）β（1）介导的细胞反应。一个Arg-Gly-Asp-independent的细胞粘附序列也被确定在cervicin-1中。抗体诱导的β（1）整合素激活增强了平滑肌细胞在β（1）整合素配体上的粘附和铺展。A375-SM黑色素瘤细胞主要通过α（v）β（3）结合含Arg-Gly-Asp的Bp 1蛋白片段，而HT 1080细胞主要使用α（5）β（1）。这项研究已经表明，β-胡萝卜素微纤维介导细胞粘附，α（5）β（1）和α（v）β（3）都是重要的但细胞特异性的β-胡萝卜素-1受体，并且与β-胡萝卜素-1的细胞相互作用影响细胞行为。
Fibrillins are the major glycoprotein components of microfibrils that form a template for tropoelastin during elastic fibrillogenesis. We have examined cell adhesion to assembled purified microfibrils, and its molecular basis. Human dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin alpha(5)beta(1) interactions with fibrillin ligands were identified, but integrin alpha(v)beta(3) also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant alpha(5)beta(1) and some alpha(v)beta(3) receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Asp-containing fibrillin-1 protein fragments induced signaling events that led to cell spreading, altered cytoskeletal organization, and enhanced extracellular fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or fibronectin implied substrate-specific alpha(5)beta(1)-mediated cellular responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin ligands was enhanced by antibody-induced beta(1) integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through alpha(v)beta(3), whereas HT1080 cells used mainly alpha(5)beta(1). This study has shown that fibrillin microfibrils mediate cell adhesion, that alpha(5)beta(1) and alpha(v)beta(3) are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior.