Institute of Vascular Medicine, Peking University Third Hospital and Academy for Advanced Interdisciplinary Studies, Peking University, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China.
Graduate School of Frontier Biosciences, Osaka University, Osaka, 5650871, Japan.
Sci Rep. 2017 Oct 20;7(1):13685. doi: 10.1038/s41598-017-06147-6.
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.
丝状伪足从细胞前缘伸出，在细胞运动中发挥重要作用。在这里，我们报告肌球蛋白 X（由 Myo10 编码）诱导多周期丝状伪足延伸的机制。我们发现肌动蛋白、Arp2/3、纽蛋白和整合素-β 首先在细胞前缘积累。然后肌球蛋白 X 聚集在这些部位，通过侧向运动逐渐聚集，并随后启动丝状伪足的形成。在丝状伪足延伸过程中，我们发现 Arp2/3 和整合素-β 沿着丝状伪足易位。Arp2/3 和整合素-β 随后定位于丝状伪足的尖端，肌球蛋白 X 从那里开始第二次延伸丝状伪足，改变延伸方向，从而产生长丝状伪足。通过 siRNA 消除整合素-β、Arp2/3 和纽蛋白显著减弱了肌球蛋白 X 诱导的长丝状伪足形成。我们提出以下机制。肌球蛋白 X 在细胞前缘的新生黏着斑处积累，肌球蛋白 X 在此处促进肌动蛋白汇聚以形成丝状伪足的基部。然后肌球蛋白 X 移动到丝状伪足的尖端，并吸引整合素-β 和 Arp2/3 以进一步进行肌动蛋白成核。位于尖端的肌球蛋白 X 然后启动丝状伪足伸长的第二轮，从而产生长丝状伪足。
