Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

Holt, Jesse R.; Zeng, Wei‐Zheng; Evans, Elizabeth L.; Woo, Seung-Hyun; Abuwarda, Hamid; Loud, Meaghan; Patapoutian, Ardem; Pathak, Madhu A.

doi:10.1016/j.bpj.2021.11.2122

Cited by 7 publications

(62 citation statements)

References 65 publications

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“…Conversely, epidermal-specific Piezo1 knockout mice demonstrated faster wound closure than controls. 31 Localized cellular retraction is accounted for by local myosin II force generation through phosphorylation by myosin light chain kinase (MLCK), which triggers Piezo1-mediated Ca 2+ flickers. 32 This then increases local myosin II phosphorylation via Ca 2+ -regulated MLCK and force generation in a feedforward loop, leading to cellular retraction and delayed wound closure.…”

Section: Wound Healingmentioning

confidence: 99%

“…32 This then increases local myosin II phosphorylation via Ca 2+ -regulated MLCK and force generation in a feedforward loop, leading to cellular retraction and delayed wound closure. 31 Another component of wound healing is ECM deposition and wound contraction by fibroblasts and myofibroblasts. 33 However, extreme fibroblastic responses during wound repair can lead to exaggerated scarring in the form of a hypertrophic scar (HS).…”

Section: Wound Healingmentioning

confidence: 99%

“…In vivo confirmation of Piezo1‐mediated wound‐edge retraction and wound‐closure impairment was demonstrated in wounded epidermal‐specific Piezo1 gain‐of‐function mice, which exhibited slower wound closure rates than controls. Conversely, epidermal‐specific Piezo1 knockout mice demonstrated faster wound closure than controls 31 . Localized cellular retraction is accounted for by local myosin II force generation through phosphorylation by myosin light chain kinase (MLCK), which triggers Piezo1‐mediated Ca 2+ flickers 32 .…”

Section: Functionsmentioning

confidence: 99%

“…Re‐epithelialization during wound closure has been shown to respond to mechanical cues and cell‐generated traction forces 29,30 . The underlying mechanistic pathways rely on Piezo1 expression and activity 31 . By imaging the spatiotemporal localization of Piezo1 channels, Holt et al 31 .…”

Section: Functionsmentioning

confidence: 99%

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A Piez-o the jigsaw: the Piezo1 channel in skin biology

Eid

Kurban

2022

Clinical and Experimental Dermatology

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The skin is the largest organ covering the entirety of the body. Its role as a physical barrier to the outside world as well as its endocrinological and immunological functions subject it to continuous internal and external mechanical forces. Thus, mechanotransduction is of the utmost importance for the skin in order to process and leverage mechanical input for its various functions. Piezo1 is a mechanosensitive ion channel that is a primary mediator of mechanotransduction and is highly expressed in the skin. The discovery of Piezo1 earned a Nobel Prize, and has had a profound impact on our understanding of physiology and pathology including paramount contributions in cutaneous biology. This review provides insight into the roles of Piezo1 in the development, physiology and pathology of the skin with a special emphasis on the molecular pathways through which it instigates these various roles. In epidermal homeostasis, Piezo1 mediates cell extrusion in conditions of overcrowding and division in conditions of low cellular density. Piezo1 also aids in orchestrating mechanosensation, DNA protection from mechanical stress and the various components of wound healing. Conversely, Piezo1 is pathologically implicated in melanoma progression, wound healing delay, cutaneous scarring and hair loss. By shedding light on these functions, we aim to unravel the potential diagnostic and therapeutic value Piezo1 might hold in the field of Dermatology.

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Section: Wound Healingmentioning

confidence: 99%

Section: Wound Healingmentioning

confidence: 99%

Section: Functionsmentioning

confidence: 99%

Section: Functionsmentioning

confidence: 99%

See 2 more Smart Citations

A Piez-o the jigsaw: the Piezo1 channel in skin biology

Eid

Kurban

2022

Clinical and Experimental Dermatology

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“…In eukaryotes, Piezo proteins act as general mechanotransducers capable of sensing forces produced by fluid displacement (1-5), tactile stimuli (6)(7)(8)(9)(10), tissue distension (11)(12)(13)(14)(15)(16)(17) and musculoskeletal movements (18)(19)(20)(21)(22). Piezo channels participate to an astonishing diversity of biological processes, including neurosensory functions (23), development (24)(25)(26)(27)(28)(29)(30), cell volume homeostasis (31)(32)(33), inflammation (34)(35)(36)(37)(38)(39)(40), and wound healing (41).…”

Section: Introductionmentioning

confidence: 99%

PIEZO1 discriminates mechanical stimuli

Özkan

Wijerathne

Gettas

et al. 2022

Preprint

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Mechanosensitive Piezo channels are anticipated to open their pore by flattening of large transmembrane domains called blades. Yet, direct experimental evidence for the coupling between blade motions and pore opening remains sparse. Here, we report unambiguous correlations between flow-induced Piezo1 opening and fluorimetric signals from conformation-sensitive probes genetically-inserted at two blade locations, one extracellular distal and the other intracellular proximal. Inhibition of gating motions near the pore with disulfide crosslinks reduced the amplitude of fluorescence signals from the most distal probe, consistent with long-range pore-blade conformational coupling. Interestingly, both probes remained fluorimetrically silent when Piezo1 opening was evoked with hypotonic shocks, cellular indentations, or application of the chemical activator Yoda1. This work provides direct experimental evidence that the Piezo1 blades act as mechanosensory domains and suggests that different mechanical stimuli activate Piezo1 through distinct mechanotransduction pathways.

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Membrane curvature governs the distribution of Piezo1 in live cells

Yang

Arnold

et al. 2022

Preprint

Self Cite

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Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells, leading to depletion of Piezo1 from filopodia. Quantification of the curvature-dependent sorting of Piezo1 directly reveals its nano-geometry in situ. Piezo1 density on filopodia increases upon activation, independent of Ca2+, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that is abolished with channel activation.

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Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

Cited by 7 publications

References 65 publications

A Piez-o the jigsaw: the Piezo1 channel in skin biology

A Piez-o the jigsaw: the Piezo1 channel in skin biology

PIEZO1 discriminates mechanical stimuli

Membrane curvature governs the distribution of Piezo1 in live cells

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