Dynamics of focal adhesions and reorganization of F-actin in VEGF-stimulated NSCs under varying differentiation states
Dynamics of focal adhesions and reorganization of F-actin in VEGF-stimulated NSCs under varying differentiation states
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不同分化状态下 VEGF 刺激的 NSC 中粘着斑的动态和 F-肌动蛋白的重组
DOI：
10.1002/jcb.24517
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发表时间：
2013-08-01
影响因子：
4
通讯作者：
Zhang, Huanxiang
中科院分区：
文献类型：
--
作者：
Lyu, Jingya;Hu, Ya'nan;Zhang, Huanxiang
神经干/祖细胞（neural stem/progenitor cells，NSCs）的精确迁移对于神经系统的神经发生和修复至关重要。然而，详细的机制尚不清楚。我们的前期研究表明，不同分化状态的神经干细胞对血管内皮生长因子（VEGF）的迁移能力不同。在这项研究中，我们证明了不同的动力学的局灶性粘连（FA）和重组的F-肌动蛋白在神经干细胞的扩展和迁移刺激血管内皮生长因子。我们发现0.5和1天分化的迁移神经干细胞比其他状态的细胞具有更多的前沿FA。此外，粘着斑激酶（FAK）和桩蛋白的磷酸化与神经干细胞的分化状态密切相关。VEGF促进FA形成，在0、0.5和1天分化的趋化细胞中在前沿产生广泛的板状伪足，但在3天分化的细胞中不产生。此外，分化1天的细胞显示出最大的不对称性之间的层和细胞后部的FA，协调细胞极化和定向迁移。延时视频分析显示，分化1天的NSCs中FA的分解和细胞尾部的脱离更快，沿着同时在前沿的FA尺寸增大，导致对VEGF的最有效的趋化反应。总的来说，这些结果表明，在神经干细胞进行定向迁移的FA和F-actin的重组的动力学与它们的分化状态密切相关，有助于这些细胞对VEGF的不同的趋化反应。J.细胞。114：1744-1759，2013. (c)2013 Wiley Periodicals，Inc.
Precise migration of neural stem/progenitor cells (NSCs) is crucially important for neurogenesis and repair in the nervous system. However, the detailed mechanisms are not clear. Our previous results showed that NSCs in varying differentiation states possess different migratory ability to vascular endothelial growth factor (VEGF). In this study, we demonstrate the different dynamics of focal adhesions (FAs) and reorganization of F-actin in NSCs during spreading and migration stimulated by VEGF. We found that the migrating NSCs of 0.5 and 1 day differentiation possess more FAs at leading edge than cells of other states. Moreover, the phosphorylation of focal adhesion kinase (FAK) and paxillin in NSCs correlates closely with their differentiation states. VEGF promotes FA formation with broad lamellipodium generation at the leading edge in chemotaxing cells of 0, 0.5, and 1 day differentiation, but not in cells of 3 days differentiation. Furthermore, cells of 1 day differentiation show a maximal asymmetry of FAs between lamella and cell rear, orchestrating cell polarization and directional migration. Time-lapse video analysis shows that the disassembly of FAs and the cell tail detachment in NSCs of 1 day differentiation are more rapid, along with the concurrent enlarged size of FAs at the leading edge, leading to the most effective chemotactic response to VEGF. Collectively, these results indicate that the dynamics of FAs and reorganization of F-actin in NSCs that undergo directional migration correlate closely with their differentiation states, contributing to the different chemotactic responses of these cells to VEGF. J. Cell. Biochem. 114: 1744-1759, 2013. (c) 2013 Wiley Periodicals, Inc.