Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Cell Sci. 2012 Dec 1;125(Pt 23):5667-76. doi: 10.1242/jcs.107490. Epub 2012 Sep 12.
Injury is an inevitable part of life, making wound healing essential for survival. In postembryonic skin, wound closure requires that epidermal cells recognize the presence of a gap and change their behavior to migrate across it. In Drosophila larvae, wound closure requires two signaling pathways [the Jun N-terminal kinase (JNK) pathway and the Pvr receptor tyrosine kinase signaling pathway] and regulation of the actin cytoskeleton. In this and other systems, it remains unclear how the signaling pathways that initiate wound closure connect to the actin regulators that help execute wound-induced cell migrations. Here, we show that chickadee, which encodes the Drosophila Profilin, a protein important for actin filament recycling and cell migration during development, is required for the physiological process of larval epidermal wound closure. After injury, chickadee is transcriptionally upregulated in cells proximal to the wound. We found that JNK, but not Pvr, mediates the increase in chic transcription through the Jun and Fos transcription factors. Finally, we show that chic-deficient larvae fail to form a robust actin cable along the wound edge and also fail to form normal filopodial and lamellipodial extensions into the wound gap. Our results thus connect a factor that regulates actin monomer recycling to the JNK signaling pathway during wound closure. They also reveal a physiological function for an important developmental regulator of actin and begin to tease out the logic of how the wound repair response is organized.
损伤是生命中不可避免的一部分，因此伤口愈合对于生存至关重要。在后胚胎期皮肤中，伤口闭合需要表皮细胞识别出存在间隙，并改变其行为以跨越它。在果蝇幼虫中，伤口闭合需要两条信号通路[Jun N-末端激酶（JNK）通路和 Pvr 受体酪氨酸激酶信号通路]和肌动蛋白细胞骨架的调节。在这和其他系统中，仍然不清楚启动伤口闭合的信号通路如何与帮助执行伤口诱导的细胞迁移的肌动蛋白调节剂连接。在这里，我们表明，chickadee 编码果蝇 Profilin，这是一种在发育过程中对于肌动蛋白丝回收和细胞迁移很重要的蛋白质，是幼虫表皮伤口闭合的生理过程所必需的。受伤后，chickadee 在靠近伤口的细胞中转录上调。我们发现 JNK，但不是 Pvr，通过 Jun 和 Fos 转录因子介导 chic 转录的增加。最后，我们表明 chic 缺陷的幼虫不能在伤口边缘形成强壮的肌动蛋白电缆，也不能形成正常的片状伪足和片状伪足进入伤口间隙。因此，我们的结果将调节肌动蛋白单体回收的因子与伤口闭合过程中的 JNK 信号通路联系起来。它们还揭示了肌动蛋白的一个重要发育调节剂的生理功能，并开始梳理伤口修复反应是如何组织的逻辑。
