Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation
Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation
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DOI：
10.1242/jcs.003954
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发表时间：
2007-04-15
影响因子：
4
通讯作者：
Kielty, Cay M.
中科院分区：
文献类型：
--
作者：
Bax, Daniel V.;Mahalingam, Yashithra;Kielty, Cay M.
我们已经定义了细胞与纤维蛋白-1黏附的分子基础，纤维蛋白-1是细胞外微纤维的主要结构成分，与弹性纤维有关。使用人皮肤成纤维细胞和含有Arg-Gly-Asp基序的重组结构域交换片段，我们已经证明了整合素α(5)β(1)介导的细胞黏附和迁移需要上游结构域。邻近的支持局部粘连形成的肝素结合位点被映射到纤维蛋白-1的TB5基序。定点突变揭示了两个精氨酸残基对肝素结合至关重要，并证实了它们在局部粘连形成中的作用。这些并列在纤维蛋白-1上的整合素和Syndecan黏附基序在进化上是保守的，使人想起纤维连接蛋白上类似的功能元件，突出了它们至关重要的功能重要性。
We have defined the molecular basis of cell adhesion to fibrillin- 1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a requirement for upstream domains for integrin-alpha(5)beta(1)- mediated cell adhesion and migration. An adjacent heparin- binding site, which supports focal adhesion formation, was mapped to the fibrillin- 1 TB5 motif. Site- directed mutagenesis revealed two arginine residues that are crucial for heparin binding, and confirmed their role in focal adhesion formation. These integrin and syndecan adhesion motifs juxtaposed on fibrillin- 1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance.