Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

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 elus...

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Autores principales:	Jesse R Holt, Wei-Zheng Zeng, Elizabeth L Evans, Seung-Hyun Woo, Shang Ma, Hamid Abuwarda, Meaghan Loud, Ardem Patapoutian, Medha M Pathak
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	mechanotransduction mechanically activated ion channels ion channel dynamics cellular retraction collective migration cell migration Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/db48aab09a994f61becdfd08aa6abd6e
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spelling	oai:doaj.org-article:db48aab09a994f61becdfd08aa6abd6e2021-11-10T13:26:15ZSpatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing10.7554/eLife.654152050-084Xe65415https://doaj.org/article/db48aab09a994f61becdfd08aa6abd6e2021-09-01T00:00:00Zhttps://elifesciences.org/articles/65415https://doaj.org/toc/2050-084XKeratinocytes, 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.Jesse R HoltWei-Zheng ZengElizabeth L EvansSeung-Hyun WooShang MaHamid AbuwardaMeaghan LoudArdem PatapoutianMedha M PathakeLife Sciences Publications Ltdarticlemechanotransductionmechanically activated ion channelsion channel dynamicscellular retractioncollective migrationcell migrationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mechanotransduction mechanically activated ion channels ion channel dynamics cellular retraction collective migration cell migration Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	mechanotransduction mechanically activated ion channels ion channel dynamics cellular retraction collective migration cell migration Medicine R Science Q Biology (General) QH301-705.5 Jesse R Holt Wei-Zheng Zeng Elizabeth L Evans Seung-Hyun Woo Shang Ma Hamid Abuwarda Meaghan Loud Ardem Patapoutian Medha M Pathak Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
description	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.
format	article
author	Jesse R Holt Wei-Zheng Zeng Elizabeth L Evans Seung-Hyun Woo Shang Ma Hamid Abuwarda Meaghan Loud Ardem Patapoutian Medha M Pathak
author_facet	Jesse R Holt Wei-Zheng Zeng Elizabeth L Evans Seung-Hyun Woo Shang Ma Hamid Abuwarda Meaghan Loud Ardem Patapoutian Medha M Pathak
author_sort	Jesse R Holt
title	Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
title_short	Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
title_full	Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
title_fullStr	Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
title_full_unstemmed	Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
title_sort	spatiotemporal dynamics of piezo1 localization controls keratinocyte migration during wound healing
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/db48aab09a994f61becdfd08aa6abd6e
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_version_	1718440046638399488

Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

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