Department of Cell Biology and Neurology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
Curr Biol. 2013 Jun 17;23(12):1046-56. doi: 10.1016/j.cub.2013.04.057. Epub 2013 Jun 6.
Actin-based cell motility is fundamental for development, function, and malignant events in eukaryotic organisms. During neural development, axonal growth cones depend on rapid assembly and disassembly of actin filaments (F-actin) for their guided extension to specific targets for wiring. Monomeric globular actin (G-actin) is the building block for F-actin but is not considered to play a direct role in spatiotemporal control of actin dynamics in cell motility.
Here we report that a pool of G-actin dynamically localizes to the leading edge of growth cones and neuroblastoma cells to spatially elevate the G-/F-actin ratio that drives membrane protrusion and cell movement. Loss of G-actin localization leads to the cessation and retraction of membrane protrusions. Moreover, G-actin localization occurs asymmetrically in growth cones during attractive turning. Finally, we identify the actin monomer-binding proteins profilin and thymosin β4 as key molecules that localize actin monomers to the leading edge of lamellipodia for their motility.
Our results suggest that dynamic localization of G-actin provides a novel mechanism to regulate the spatiotemporal actin dynamics underlying membrane protrusion in cell locomotion and growth cone chemotaxis.
基于肌动蛋白的细胞运动对于真核生物的发育、功能和恶性事件是基础。在神经发育过程中，轴突生长锥依赖于肌动蛋白丝（F-肌动蛋白）的快速组装和拆卸，以将其引导到特定的靶标进行布线。单体球状肌动蛋白（G-肌动蛋白）是 F-肌动蛋白的构建块，但不被认为在细胞运动中肌动蛋白动力学的时空控制中发挥直接作用。
在这里，我们报告了一个 G-肌动蛋白池在生长锥和神经母细胞瘤细胞的前缘动态定位，以空间上增加驱动膜突和细胞运动的 G-/F-肌动蛋白比率。G-肌动蛋白定位的丧失导致膜突的停止和缩回。此外，在有吸引力的转弯过程中，G-肌动蛋白在生长锥中不对称定位。最后，我们确定了肌动蛋白单体结合蛋白原肌球蛋白和胸腺素β4是将肌动蛋白单体定位到片状伪足前缘以促进其运动的关键分子。
我们的结果表明，G-肌动蛋白的动态定位为调节细胞运动和生长锥趋化性中膜突下的肌动蛋白动力学时空提供了一种新机制。
