The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin
The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin
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DOI：
10.1182/blood-2005-07-2961
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Luo, Y
中科院分区：
文献类型：
--
作者：
Huang, Y;Shi, H;Luo, Y
核仁素最初被描述为核蛋白，最近发现在血管生成过程中表达于内皮细胞表面。然而，细胞表面核仁素在血管生成中的功能仍然是个谜。在这里，我们报告说，内皮细胞粘附细胞外基质成分，血管内皮生长因子（VEGF）动员核仁素从细胞核到细胞表面。功能性阻断或下调内皮细胞中细胞表面核仁素的表达可显著抑制内皮细胞的迁移并阻止毛细血管小管的形成。此外，非肌肉肌球蛋白重链9（MyH9），肌动蛋白为基础的马达蛋白，被确定为核仁结合蛋白。随后的研究表明，MyH9作为核仁素和细胞骨架之间的物理接头，从而调节核仁素的易位。敲低内源性MyH9，特异性抑制肌球蛋白活性，或过表达功能缺陷型MyH9，破坏细胞表面核仁素的组织并抑制其血管生成功能。这些研究表明，VEGF，细胞外基质，和细胞内马达蛋白MyH9都是必不可少的新功能的核仁素在血管生成。
Nucleolin, originally described as a nuclear protein, was recently found to be expressed on the surface of endothelial cells during angiogenic. However, the functions of cell-surface nucleolin in angiogenic remain mysterious. Here we report that upon endothelial cells adhering to extracellular matrix components, vascular endothelial growth factor (VEGF) mobilizes nucleolin from nucleus to cell surface. Functional blockage or downregulation of the expression of cell-surface nucleolin in endothelial cells significantly inhibits the migration of endothelial cells and prevents capillary-tubule formation. Moreover, nonmuscle myosin heavy chain 9 (MyH9), an actin-based motor protein, is identified as a nucleolin-binding protein. Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin. Knocking down endogenous MyH9, specifically inhibiting myosin activity, or overexpressing functional deficient MyH9 disrupts the organization of cell-surface nucleolin and inhibits its angiogenic function. These studies indicate that VEGF, extracellular matrix, and intracellular motor protein MyH9 are all essential for the novel function of nucleolin in angiogenic.