Structural Biology: Piezo Senses Tension through Curvature

Liang, Xin; Howard, Jonathon

doi:10.1016/j.cub.2018.02.078

Cited by 33 publications

(35 citation statements)

References 19 publications

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“…Altogether, these findings indicate that Piezo1 might sense membrane tension through a change in its curvature (Guo and MacKinnon, 2017;Liang and Howard, 2018) (Figures 4B-D). Indeed, recent cryo-electron microscopy observations, as well as atomic force microscopy analysis demonstrate that Piezo1 can be flattened reversibly into the membrane plane (Lin et al, 2019).…”

Section: Sensing Force By a Change In Piezo1 Curvaturementioning

confidence: 63%

“…MSCs. If the MSC in the bilayer is approximated to a cylindrical plug, the free energy difference between the open and closed states (G = G0-TA) is given by G0 [the difference in the absence of force] minus membrane tension (T) times the change in cross-sectional channel area occurring between the closed and the open state [A] (Liang and Howard, 2018;Sachs and Morris, 1998).…”

Section: Activation Of Mscs By Membrane Tensionmentioning

confidence: 99%

“…Furthermore, mechanical calculations predict that Piezo1 will shape the membrane into a curved "membrane footprint", thus influencing the mechanics of the bilayer at a distance from the channel and amplifying the mechanosensitivity of Piezo1 in the low tensional range (Haselwandter and MacKinnon, 2018). It is hypothesized that Piezo1 may sense membrane tension though a flattening, with a consequent large increase in the in-plane channel area (A) (Haselwandter and MacKinnon, 2018;Liang and Howard, 2018) (Figure 4D). If Piezo1 becomes completely flat in response to an increase in tension, its cross-sectional area (A) is expected to increase by 120 nm 2 (versus 20 nm 2 for MscL and 4.8 nm 2 for TRAAK).…”

Section: Sensing Force By a Change In Piezo1 Curvaturementioning

confidence: 99%

“…This estimated large increase in A is predicted to confer exquisite mechanosensitivity to Piezo1 (i.e. the driving energy -T is high), despite the fact that Piezo1 has a small ionic pore (35 pS) (Liang and Howard, 2018).…”

Section: Sensing Force By a Change In Piezo1 Curvaturementioning

confidence: 99%

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Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Douguet

Honoré

2019

Cell

156

128

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The conversion of force into an electrical cellular signal is mediated by the opening of different types of mechanosensitive ion channels (MSCs), including TREK/TRAAK K 2P channels, Piezo1/2, TMEM63/OSCA and TMC1/2. Mechanoelectrical transduction plays a key role in hearing, balance, touch, proprioception and is also implicated in the autonomic regulation of blood pressure and breathing. Thus, dysfunction of MSCs is associated with a variety of inherited and acquired disease states. Significant progress has recently been made in identifying these channels, solving their structure and understanding the gating of both hyperpolarizing and depolarizing MSCs. Besides prototypical activation by membrane tension, additional gating mechanisms involving channel curvature and/or tethered elements are at play.

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Section: Sensing Force By a Change In Piezo1 Curvaturementioning

confidence: 63%

Section: Activation Of Mscs By Membrane Tensionmentioning

confidence: 99%

Section: Sensing Force By a Change In Piezo1 Curvaturementioning

confidence: 99%

Section: Sensing Force By a Change In Piezo1 Curvaturementioning

confidence: 99%

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Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Douguet

Honoré

2019

Cell

156

128

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“…An RBPMS repressed exon lies within the conserved Piezo domain immediately adjacent to the mechanosensing "beam" (Liang & Howard, 2018). ECM components affected by RBPMS include fibronectin (FN1), which interacts directly with integrins, and HSPG2 ( Fig.…”

Section: Rbpms Targets Numerous Mrnas Important For Smc Functionmentioning

confidence: 99%

Identification of RBPMS as a smooth muscle master splicing regulator via proximity of its gene with super-enhancers

Nakagaki-Silva

Gooding

Llorian

et al. 2019

Preprint

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Alternative splicing (AS) programs are primarily controlled by regulatory RNA binding proteins (RBPs). It has been proposed that a small number of master splicing regulators might control cell-specific splicing networks and that these RBPs could be identified by proximity of their genes to transcriptional super-enhancers. Using this approach we identified RBPMS as a critical splicing regulator in differentiated vascular smooth muscle cells (SMCs). RBPMS is highly down-regulated during phenotypic switching of SMCs from a contractile to a motile and proliferative phenotype and is responsible for 20% of the AS changes during this transition. RBPMS directly regulates AS of numerous components of the actin cytoskeleton and focal adhesion machineries whose activity is critical for SMC function in both phenotypes. RBPMS also regulates splicing of other splicing, post-transcriptional and transcription regulators including the key SMC transcription factor Myocardin, thereby matching many of the criteria of a master regulator of AS in SMCs.

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Recent advances in the pathophysiology of PIEZO1‐related hereditary xerocytosis

et al. 2021

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Hereditary xerocytosis is a rare red blood cell disease related to gain-of-function mutations in the FAM38A gene, encoding PIEZO1, in 90% of cases; PIEZO1 is a broadly expressed mechano-transducer that plays a major role in many cell systems and tissues that respond to mechanical stress. In erythrocytes, PIEZO1 adapts the intracellular ionic content and cell hydration status to the mechanical constraints induced by the environment. Until recently, the pathophysiology of hereditary xerocytosis was mainly believed to be based on the "PIEZO1-Gardos channel axis" in erythrocytes, according to which PIEZO1-activating mutations induce a calcium influx that secondarily activates the Gardos channel, leading to potassium and water efflux and subsequently to red blood cell dehydration. However, recent studies have demonstrated additional roles for PIEZO1 during early erythropoiesis and reticulocyte maturation, as well as roles in other tissues and cells such as lymphatic vessels, hepatocytes, macrophages and platelets that may affect the pathophysiology of the disease. These findings, presented and discussed in this review, broaden our understanding of hereditary xerocytosis beyond that of primarily being a red blood cell disease and identify potential therapeutic targets. | INTRODUCTIONThe PIEZO proteins are a family of mechano-transducers first described in a neuron derived cell line in 2010. 1 The two members are PIEZO1, encoded by FAM38A on chromosome 16, and PIEZO2, encoded by FAM38B on chromosome 18. They are expressed in many tissues. 1,2 The structure of PIEZO1 has been recently elucidated. A first description of the murine protein revealed its three-dimensional structure, consisting of a three-bladed homotrimeric transmembrane helix completed by an extracellular cap. An intra-cytoplasmic domain, split into three parts, called "beams," extends from the transmembrane domain. The C-terminal end of each monomer has an extracellular domain (ECD), which forms the cap, and an intracellular domain (CTD), which appears to be connected to the paddles by the beams and closes the inner ion pore (Figure 1). The assembly provides a hydrophilic central transmembrane duct bordered by six helices that allows the passage of ions. Thus PIEZO1 constitutes a mechanosensitive ion channel due to the flexibility of the three blades. 1 Deformation of the plasma membrane subsequent to mechanical stimulation induces rotation of the PIEZO1 blades, transmitting such deformation to the ECD and CTD domains, allowing the ion channel to open using a lever-like mechanism. 2 When a compressive force is applied parallel to the axis of the ion channel, it induces lateral membrane tension, resulting in flattening and widening of PIEZO1, which causes the pore to open and allows the passage of ions. Such deformations are reversible, and PIEZO1 returns rapidly to its original conformation. [3][4][5] After opening, PIEZO1 acts as a passive channel for mono/divalent cations depending on their extracellular-intracellular Nicolas Jankovsky and Alexis Caulier...

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Structural Biology: Piezo Senses Tension through Curvature

Cited by 33 publications

References 19 publications

Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Identification of RBPMS as a smooth muscle master splicing regulator via proximity of its gene with super-enhancers

Recent advances in the pathophysiology of PIEZO1‐related hereditary xerocytosis

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