Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
J Cell Sci. 2013 Nov 1;126(Pt 21):5005-17. doi: 10.1242/jcs.133421. Epub 2013 Aug 28.
Embryonic wound healing provides a perfect example of efficient recovery of tissue integrity and homeostasis, which is vital for survival. Tissue movement in embryonic wound healing requires two functionally distinct actin structures: a contractile actomyosin cable and actin protrusions at the leading edge. Here, we report that the discrete formation and function of these two structures is achieved by the temporal segregation of two intracellular upstream signals and distinct downstream targets. The sequential activation of ERK and phosphoinositide 3-kinase (PI3K) signalling divides Xenopus embryonic wound healing into two phases. In the first phase, activated ERK suppresses PI3K activity, and is responsible for the activation of Rho and myosin-2, which drives actomyosin cable formation and constriction. The second phase is dominated by restored PI3K signalling, which enhances Rac and Cdc42 activity, leading to the formation of actin protrusions that drive migration and zippering. These findings reveal a new mechanism for coordinating different modes of actin-based motility in a complex tissue setting, namely embryonic wound healing.
胚胎创伤愈合为组织完整性和动态平衡的有效恢复提供了一个完美的范例，这对生存至关重要。胚胎创伤愈合中的组织运动需要两种功能上不同的肌动蛋白结构：收缩性肌球蛋白缆线和前缘处的肌动蛋白突起。在这里，我们报告说，这两种结构的离散形成和功能是通过两个细胞内上游信号和不同的下游靶标的时间分离来实现的。ERK 和磷酸肌醇 3-激酶 (PI3K) 信号的顺序激活将非洲爪蟾胚胎创伤愈合分为两个阶段。在第一阶段，激活的 ERK 抑制 PI3K 活性，负责激活 Rho 和肌球蛋白-2，从而驱动肌球蛋白缆线的形成和收缩。第二阶段主要由恢复的 PI3K 信号主导，该信号增强 Rac 和 Cdc42 活性，导致形成肌动蛋白突起，从而驱动迁移和拉链运动。这些发现揭示了一种在复杂组织环境中协调不同形式的基于肌动蛋白的运动的新机制，即胚胎创伤愈合。
