Autocrine Insulin Pathway Signaling Regulates Actin Dynamics In Cell Wound Repair

Author summaryOrganisms are constantly subject to damage by physiological and environmental stresses at the cell, tissue, and organ levels. While organisms have robust repair systems to survive from such damage, the underlying molecular mechanisms for these different scales of repair are different. Using microarray analyses and pharmacological assays with the Drosophila model, we examined the requirements for transcription and translation during cell wound repair. We find that translation, rather than transcription, is needed for the initial steps of cell wound repair. Transcription is required for the later steps of the repair process. We have successfully identified and verified 80 up-regulated and 173 down-regulated genes, most of which are new players in cell wound repair. A number of these genes function to regulate cytoskeleton dynamics at different steps of cell repair process. Interestingly, a subset of these genes encode components of the insulin signaling pathway. While insulin signaling is required for tissue and organ wound repair, we find that a canonical insulin pathway is activated upon wounding in the repair of individual cells as well. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.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.