Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function
Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function
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DOI：
10.1091/mbc.e14-02-0712
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发表时间：
2014-09-01
影响因子：
3.3
通讯作者：
Gertler, Frank B.
中科院分区：
文献类型：
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作者：
Barzik, Melanie;McClain, Leslie M.;Gertler, Frank B.
丝状伪足是细胞质膜的一种延伸，在伸展和迁移的细胞中参与形成粘附、收缩和膨胀的肌动蛋白结构。由不同分子机制形成的丝状伪足是否同样支持这些细胞功能尚未解决。我们使用启用/血管扩张剂刺激的磷蛋白（Ena/VASP）缺陷的MVD 7成纤维细胞，这也是缺乏内源性mDia 2，作为一个模型系统来研究这些不同的肌动蛋白调节蛋白如何影响丝状伪足形态和动力学相互独立。由Ena/VASP或mDia 2启动的丝状伪足包含类似的分子库存，但在参数如数量、长度、F-肌动蛋白组织、寿命和持续性方面存在显著差异。此外，在缺乏Ena/VASP的情况下，mDia 2产生的丝状伪足不支持粘附和随后的板状伪足延伸所需的整合素依赖性信号级联的启动，从而导致早期细胞铺展的缺陷。VASP与组成型活性mDia 2（M/A）的共表达挽救了这些早期粘连缺陷。我们的结论是，Ena/VASP和mDia 2支持的丝状伪足的形成具有显着不同的属性和Ena/VASP调节mDia 2启动丝状伪足的形态，动力学和功能。
Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP)-deficient MVD7 fibroblasts, which are also devoid of endogenous mDia2, as a model system to investigate how these different actin regulatory proteins affect filopodia morphology and dynamics independently of one another. Filopodia initiated by either Ena/VASP or mDia2 contained similar molecular inventory but differed significantly in parameters such as number, length, F-actin organization, lifetime, and protrusive persistence. Moreover, in the absence of Ena/VASP, filopodia generated by mDia2 did not support initiation of integrin-dependent signaling cascades required for adhesion and subsequent lamellipodial extension, thereby causing a defect in early cell spreading. Coexpression of VASP with constitutively active mDia2(M/A) rescued these early adhesion defects. We conclude that Ena/VASP and mDia2 support the formation of filopodia with significantly distinct properties and that Ena/VASP regulates mDia2-initiated filopodial morphology, dynamics, and function.