Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS One. 2012;7(8):e41342. doi: 10.1371/journal.pone.0041342. Epub 2012 Aug 2.
Productive protrusions allowing motile cells to sense and migrate toward a chemotactic gradient of reactive oxygen species (ROS) require a tight control of the actin cytoskeleton. However, the mechanisms of how ROS affect cell protrusion and actin dynamics are not well elucidated yet. We show here that ROS induce the formation of a persistent protrusion. In migrating epithelial cells, protrusion of the leading edge requires the precise regulation of the lamellipodium and lamella F-actin networks. Using fluorescent speckle microscopy, we showed that, upon ROS stimulation, the F-actin retrograde flow is enhanced in the lamellipodium. This event coincides with an increase of cofilin activity, free barbed ends formation, Arp2/3 recruitment, and ERK activity at the cell edge. In addition, we observed an acceleration of the F-actin flow in the lamella of ROS-stimulated cells, which correlates with an enhancement of the cell contractility. Thus, this study demonstrates that ROS modulate both the lamellipodium and the lamella networks to control protrusion efficiency.
活性氧（ROS）趋化梯度能使游动细胞感知并迁移，这需要对肌动蛋白细胞骨架进行严格的控制。然而，ROS 如何影响细胞突起和肌动蛋白动力学的机制尚不清楚。我们在这里表明，ROS 诱导形成持久的突起。在迁移的上皮细胞中，前缘的突起需要精细调节片状伪足和片层 F-肌动蛋白网络。使用荧光斑点显微镜，我们表明，在 ROS 刺激下，片状伪足中的 F-肌动蛋白逆行流动增强。这一事件与肌动蛋白丝解聚蛋白（cofilin）活性增加、游离的暴露出的 F-肌动蛋白末端形成、ARP2/3 募集和 ERK 活性在细胞边缘的增加同时发生。此外，我们观察到 ROS 刺激的细胞中 F-肌动蛋白在片层中的流动加速，这与细胞收缩性的增强相关。因此，这项研究表明，ROS 调节片状伪足和片层网络来控制突起效率。
