Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
Genomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
PLoS Genet. 2020 Dec 11;16(12):e1009186. doi: 10.1371/journal.pgen.1009186. eCollection 2020 Dec.
Cells are exposed to frequent mechanical and/or chemical stressors that can compromise the integrity of the plasma membrane and underlying cortical cytoskeleton. The molecular mechanisms driving the immediate repair response launched to restore the cell cortex and circumvent cell death are largely unknown. Using microarrays and drug-inhibition studies to assess gene expression, we find that initiation of cell wound repair in the Drosophila model is dependent on translation, whereas transcription is required for subsequent steps. We identified 253 genes whose expression is up-regulated (80) or down-regulated (173) in response to laser wounding. A subset of these genes were validated using RNAi knockdowns and exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that the canonical insulin signaling pathway controls actin dynamics through the actin regulators Girdin and Chickadee (profilin), and its disruption leads to abnormal wound repair. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.
细胞经常受到机械和/或化学应激源的影响，这些应激源会损害质膜和下伏皮质细胞骨架的完整性。驱动启动以修复细胞皮质并避免细胞死亡的即时修复反应的分子机制在很大程度上尚不清楚。使用微阵列和药物抑制研究来评估基因表达，我们发现果蝇模型中细胞伤口修复的启动依赖于翻译，而转录是随后步骤所必需的。我们鉴定了 253 个基因，这些基因的表达在受到激光损伤后上调（80 个）或下调（173 个）。使用 RNAi 敲低验证了这些基因中的一部分，它们表现出异常的肌动球蛋白环组装和/或肌动蛋白重塑缺陷。引人注目的是，我们发现经典的胰岛素信号通路通过肌动蛋白调节因子 Girdin 和 Chickadee（原肌球蛋白）控制肌动蛋白动力学，其破坏会导致异常的伤口修复。我们的研究结果为理解健康个体和涉及伤口愈合缺陷的疾病患者中细胞伤口修复的进展提供了新的见解。
