Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.
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DOI:
10.1038/s41598-017-06147-6
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发表时间:
2017-10-20
期刊:
影响因子:
4.6
通讯作者:
Ikebe M
Ikebe M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
He K;Sakai T;Tsukasaki Y;Watanabe TM;Ikebe M

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丝状伪足突出于细胞的前缘,在细胞运动中起重要作用。在这里,我们报告肌球蛋白X(编码Myo 10)诱导的多周期丝状伪足延伸的机制。我们发现肌动蛋白、Arp 2/3、黏着斑蛋白和整合素β首先聚集在细胞的前缘。肌球蛋白X然后聚集在这些网站,逐渐聚集的横向运动,随后开始丝状伪足的形成。在丝状伪足延伸过程中,我们发现Arp 2/3和整合素β沿着丝状伪足移位。Arp 2/3和整合素β定位于丝状伪足的顶端,肌球蛋白X从此处开始丝状伪足的第二次延伸并改变延伸方向,从而产生长丝状伪足。通过siRNA消除整合素-β、Arp 2/3和黏着斑蛋白显著减弱肌球蛋白-X诱导的长丝状伪足形成。我们提出以下机制。肌球蛋白X在细胞前缘的新生粘着灶处积累,在那里肌球蛋白X促进肌动蛋白会聚以产生丝状伪足的基部。然后肌球蛋白X移动到丝状伪足尖端并吸引整合素-β和Arp 2/3用于进一步的肌动蛋白成核。位于尖端的肌球蛋白X然后启动第二周期的丝状伪足伸长,以产生长丝状伪足。
Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell’s leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell’s leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.
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