Apr 7, 2020

Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair

BioRxiv : the Preprint Server for Biology
M. NakamuraSusan 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 that is launched to restore the cell cortex and circumvent cell death are largely unknown. Using drug-inhibition studies and microarray analyses in the Drosophila model, we find that initiation of cell wound repair is dependent on translation, whereas transcription is required for subsequent steps in the process. 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 found to exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that disruption of the canonical insulin signaling pathway leads to abnormal wound repair, and that it controls actin dynamics through the actin regulators Girdin and Chickadee (profilin). 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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