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bioRxiv · 10.1101/2020.10.18.344598

PIEZO1-induced cellular retraction controls keratinocyte migration in wound healing

Holt, J. R.·Zeng, W.-Z.·Evans, E. L.·Woo, S.-H.·Ma, S.·Abuwarda, H.·Loud, M.·Patapoutian, A.·Pathak, M. M.
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Abstract

Keratinocytes, the predominant cell type of the epidermis, migrate to reinstate the epithelial barrier during wound healing. Mechanical cues are known to regulate keratinocyte re-epithelization and wound healing however, the underlying molecular transducers and biophysical mechanisms remain elusive. Here, we show through molecular, cellular and organismal studies that the mechanically-activated ion channel PIEZO1 regulates keratinocyte migration and wound healing. Epidermal-specific Piezo1 knockout mice exhibited faster wound closure while gain-of-function mice displayed slower wound closure compared to littermate controls. By imaging the spatiotemporal localization dynamics of endogenous PIEZO1 channels we find that channel enrichment in sub-cellular regions induces a localized cellular retraction that slows keratinocyte migration. Our findings suggest a potential pharmacological target for wound treatment. More broadly, we show that nanoscale spatiotemporal dynamics of Piezo1 channels can control tissue-scale events, a finding with implications beyond wound healing to processes as diverse as development, homeostasis, disease and repair.

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Holt, J. R., Zeng, W.-Z., Evans, E. L., Woo, S.-H., Ma, S., Abuwarda, H., Loud, M., Patapoutian, A., Pathak, M. M.. 2020-10-19. PIEZO1-induced cellular retraction controls keratinocyte migration in wound healing. https://doi.org/10.1101/2020.10.18.344598

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