Structure of the mechanically activated ion channel Piezo1

Saotome, Kei; Murthy, Swetha E.; Kefauver, Jennifer M.; Whitwam, Tess; Patapoutian, Ardem; Ward, Andrew B.

doi:10.1038/nature25453

Cited by 448 publications

(459 citation statements)

References 52 publications

(72 reference statements)

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“…3D, Fig. S10), confirming that PIEZO1 responds to local, not global, membrane tension (Saotome et al, 2017). Sequential tether pulling from different locations of the same cell led to local Ca 2+ influx at each pulling location but not at the previously pulled site, further demonstrating sub-cellular compartmentalization of mechanosensation (Fig.…”

Section: Resultsmentioning

confidence: 54%

Cell Membranes Resist Flow

Shi

Graber

Baumgart

et al. 2018

Cell

290

292

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SUMMARY The fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds, mediating long-range signaling. Here we show that propagation of membrane tension occurs quickly in cell-attached blebs, but is largely suppressed in intact cells. The failure of tension to propagate in cells is explained by a fluid dynamical model that incorporates the flow resistance from cytoskeleton-bound transmembrane proteins. Perturbations to tension propagate diffusively, with a diffusion coefficient Dσ ~ 0.024 μm2/s in HeLa cells. In primary endothelial cells, local increases in membrane tension lead only to local activation of mechanosensitive ion channels and to local vesicle fusion. Thus membrane tension is not a mediator of long-range intra-cellular signaling, but local variations in tension mediate distinct processes in sub-cellular domains.

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Section: Resultsmentioning

confidence: 54%

Cell Membranes Resist Flow

Shi

Graber

Baumgart

et al. 2018

Cell

290

292

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“…Their activity have already been shown to be highly dependent on the membrane stiffening [58] and thus the membrane chol content, but also on the level of fatty acid saturation [59]. Moreover, new insights in Piezo1 structure evidenced a bend in its transmembrane section [60], whose stabilization energy might be partly compensated by the surrounding lipids. Based on the results presented in this article, we suggest that GM1/PC/chol-enriched domains could contribute to the regulation of Piezo1 by modulating its environment biophysical properties to allow an efficient and transient calcium influx.…”

Section: Lipid Domains As Modulators Of Piezo1 and Pmca Membrane Locamentioning

confidence: 99%

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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Background/Aims: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Methods: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Results: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Conclusion: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated.

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“…MSCs are mechanosensitive, and mechanical forces can induce ATP release, but the mechanisms for mechanical induction of ATP release from MSCs remain poorly understood . The Ca 2+ ‐permeable Piezo1 channel is a newly discovered mechanosensing mechanism in many types of cells . Furthermore, recent studies have reported that mechanical or chemical activation of the Piezo1 channel induces ATP release from endothelial cells, urothelial cells, and red blood cells .…”

Section: Introductionmentioning

confidence: 99%

Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling

Mousawi

Peng

et al. 2020

Stem Cells

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In this study, we examined the Ca2+‐permeable Piezo1 channel, a newly identified mechanosensing ion channel, in human dental pulp‐derived mesenchymal stem cells (MSCs) and hypothesized that activation of the Piezo1 channel regulates MSC migration via inducing ATP release and activation of the P2 receptor purinergic signaling. The Piezo1 mRNA and protein were readily detected in hDP‐MSCs from multiple donors and, consistently, brief exposure to Yoda1, the Piezo1 channel‐specific activator, elevated intracellular Ca2+ concentration. Yoda1‐induced Ca2+ response was inhibited by ruthenium red or GsMTx4, two Piezo1 channel inhibitors, and also by Piezo1‐specific siRNA. Brief exposure to Yoda1 also induced ATP release. Persistent exposure to Yoda1 stimulated MSC migration, which was suppressed by Piezo1‐specific siRNA, and also prevented by apyrase, an ATP scavenger, or PPADS, a P2 generic antagonist. Furthermore, stimulation of MSC migration induced by Yoda1 as well as ATP was suppressed by PF431396, a PYK2 kinase inhibitor, or U0126, an inhibitor of the mitogen‐activated protein kinase MEK/ERK signaling pathway. Collectively, these results suggest that activation of the Piezo1 channel stimulates MSC migration via inducing ATP release and subsequent activation of the P2 receptor purinergic signaling and downstream PYK2 and MEK/ERK signaling pathways, thus revealing novel insights into the molecular and signaling mechanisms regulating MSC migration. Such findings provide useful information for evolving a full understanding of MSC migration and homing and developing strategies to improve MSC‐based translational applications.

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Structure of the mechanically activated ion channel Piezo1

Cited by 448 publications

References 52 publications

Cell Membranes Resist Flow

Cell Membranes Resist Flow

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling

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