Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

eLife

Elizabeth L Evans¹  Hamid Abuwarda¹  Jesse R Holt²  Medha M Pathak³  Seung-Hyun Woo⁴  Shang Ma⁴  Ardem Patapoutian⁴  Wei-Zheng Zeng⁴  Meaghan Loud⁴ 

[1] Departmentof Physiology & Biophysics, UC Irvine, Irvine, United States;Sue and Bill Gross Stem Cell Research Center, UC Irvine, Irvine, United States;Departmentof Physiology & Biophysics, UC Irvine, Irvine, United States;Sue and Bill Gross Stem Cell Research Center, UC Irvine, Irvine, United States;Center for Complex Biological Systems, UC Irvine, Irvine, United States;Departmentof Physiology & Biophysics, UC Irvine, Irvine, United States;Sue and Bill Gross Stem Cell Research Center, UC Irvine, Irvine, United States;Center for Complex Biological Systems, UC Irvine, Irvine, United States;Department of Biomedical Engineering, UC Irvine, Irvine, United States;Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, United States;

关键词: mechanotransduction;    mechanically activated ion channels;    ion channel dynamics;    cellular retraction;    collective migration;    cell migration;    Mouse;   

DOI  :  10.7554/eLife.65415

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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-epithelialization 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 at some regions of the wound edge induces a localized cellular retraction that slows keratinocyte collective migration. In migrating single keratinocytes, PIEZO1 is enriched at the rear of the cell, where maximal retraction occurs, and we find that chemical activation of PIEZO1 enhances retraction during single as well as collective migration. Our findings uncover novel molecular mechanisms underlying single and collective keratinocyte migration that may 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.

【 授权许可】

CC BY