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Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair

by Mitsutoshi Nakamura, Jeffrey M. Verboon, Tessa E. Allen, Maria Teresa Abreu-Blanco, Raymond Liu, Andrew N. M. Dominguez, Jeffrey J. Delrow, Susan M. Parkhurst

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.

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https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009186

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