Extracellular Alix regulates integrin-mediated cell adhesions and extracellular matrix assembly.
Extracellular Alix regulates integrin-mediated cell adhesions and extracellular matrix assembly.
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细胞外 Alix 调节整合素介导的细胞粘附和细胞外基质组装。
DOI：
10.1038/emboj.2008.134
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Kuang,Jian
中科院分区：
文献类型：
--
作者：
Pan,Shujuan;Wang,Ruoning;Zhou,Xi;Corvera,Joe;Kloc,Malgorzata;Sifers,Richard;Gallick,GaryE;Lin,Sue-Hwa;Kuang,Jian
阿利克斯（ALG-2相互作用蛋白X）是一种参与内体分选和肌动蛋白细胞骨架组装的细胞质衔接蛋白，是维持成纤维细胞形态所必需的。由于阿利克斯与溶组织内阿米巴中的粘附素具有序列相似性，并且我们观察到阿利克斯是分泌的，因此我们确定细胞外阿利克斯是否影响成纤维细胞形态。在这里，我们证明了分泌的阿利克斯沉积在非永生化的WI 38成纤维细胞的基质上。抗体与细胞外阿利克斯的结合延缓了WI 38细胞在纤连蛋白和玻连蛋白上的粘附和铺展。WI 38细胞中的阿利克斯敲低减少了铺展和纤连蛋白组装，并且该效果通过在细胞基质上包被重组阿利克斯而部分地得到补充。永生化NIH/3 T3成纤维细胞存款较少的阿利克斯在基质上，并有缺陷的α5β1-整合素功能。将重组阿利克斯包被在NIH/3 T3细胞的培养基质上促进α5β1-整合素介导的细胞粘附和纤连蛋白组装，这些作用需要阿利克斯的aa 605-709区域。这些结果表明，阿利克斯亚群定位于细胞外并调节整合素介导的细胞粘附和纤连蛋白基质组装。
Alix (ALG‐2‐interacting protein X), a cytoplasmic adaptor protein involved in endosomal sorting and actin cytoskeleton assembly, is required for the maintenance of fibroblast morphology. As Alix has sequence similarity to adhesin inEntamoeba histolytica, and we observed that Alix is secreted, we determined whether extracellular Alix affects fibroblast morphology. Here, we demonstrate that secreted Alix is deposited on the substratum of non‐immortalized WI38 fibroblasts. Antibody binding to extracellular Alix retards WI38 cell adhesion and spreading on fibronectin and vitronectin. Alix knockdown in WI38 cells reduces spreading and fibronectin assembly, and the effect is partially complemented by coating recombinant Alix on the cell substratum. Immortalized NIH/3T3 fibroblasts deposit less Alix on the substratum and have defects in α5β1‐integrin functions. Coating recombinant Alix on the culture substratum for NIH/3T3 cells promotes α5β1‐integrin‐mediated cell adhesions and fibronectin assembly, and these effects require the aa 605–709 region of Alix. These findings demonstrate that a sub‐population of Alix localizes extracellularly and regulates integrin‐mediated cell adhesions and fibronectin matrix assembly.