Mechanoprotection by Polycystins against Apoptosis Is Mediated through the Opening of Stretch-Activated K2P Channels

Peyronnet, Rémi; Sharif‐Naeini, Reza; Folgering, Joost H.A.; Arhatte, Malika; Jodar, Martine; Boustany, Charbel El; Gallian, Claire; Tauc, Michel; Duranton, Christophe; Rubera, Isabelle; Lesage, Florian; Pei, York; Peters, Dorien J.M.; Somlo, Stefan; Sachs, Frederick; Patel, Amanda; Honoré, Eric; Duprat, Fabrice

doi:10.1016/j.celrep.2012.01.006

Cited by 50 publications

(53 citation statements)

References 66 publications

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“…Importantly, the primary cilium is relatively small in proportion to the entire cell (less than 1 um in width and a ∼10 um in length) and neither PKD1 nor PKD2 have been shown to be mechanically activated in heterologous expression systems (DeCaen et al, 2013; Delling et al, 2013; Peyronnet et al, 2012). Application of fluid shear stress to MDCK cells leads to ATP release and calcium influx into the cytoplasm via activation of P2XR and P2YR (Rodat-Despoix et al, 2013).…”

Section: Candidate Gene Familiesmentioning

confidence: 99%

“…In smooth muscle cells, the heteromeric PKD1/PKD2 complex can regulate the activity of a stretch activated cation channel through an interaction with the actin cytoskeleton (Sharif-Naeini et al, 2009). In renal epithelial cells, PKD1 and PKD2 interact with the stretch activated potassium channels TREK-1 and TRAAK to protect against mechanical strain induced apoptosis (Peyronnet et al, 2012). In these cells, PKD1/PKD2 can also modulate the stretch induced activation of Piezo1 (Peyronnet et al, 2013).…”

Section: Candidate Gene Familiesmentioning

confidence: 99%

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Mechanically Activated Ion Channels

Ranade

Syeda

Patapoutian

2015

Neuron

545

465

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Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.

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Section: Candidate Gene Familiesmentioning

confidence: 99%

Section: Candidate Gene Familiesmentioning

confidence: 99%

Mechanically Activated Ion Channels

Ranade

Syeda

Patapoutian

2015

Neuron

545

465

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“…Electrophysiology. Electrophysiological procedure has been previously described elsewhere [24,32]. Renal mechanotransduction R. Peyronnet et al scientific report…”

Section: Methodsmentioning

confidence: 99%

Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells

et al. 2013

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Mechanical forces associated with fluid flow and/or circumferential stretch are sensed by renal epithelial cells and contribute to both adaptive or disease states. Non-selective stretch-activated ion channels (SACs), characterized by a lack of inactivation and a remarkably slow deactivation, are active at the basolateral side of renal proximal convoluted tubules. Knockdown of Piezo1 strongly reduces SAC activity in proximal convoluted tubule epithelial cells. Similarly, overexpression of Polycystin-2 (PC2) or, to a greater extent its pathogenic mutant PC2-740X, impairs native SACs. Moreover, PC2 inhibits exogenous Piezo1 SAC activity. PC2 coimmunoprecipitates with Piezo1 and deletion of its N-terminal domain prevents both this interaction and inhibition of SAC activity. These findings indicate that renal SACs depend on Piezo1, but are critically conditioned by PC2.

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“…tension (23,24), and their mechanosensitivity is thought to be important for many diverse physiological processes, including electromechanical feedback in the heart, cell volume regulation and perception of shear flow stress in epithelial tissues, pressureinduced vasorelaxation in endothelia, and even cell migration (25)(26)(27)(28). Crystal structures are also now available for these three channels in multiple conformations (29)(30)(31)(32); thus, they provide an excellent opportunity to investigate the molecular mechanisms underlying mechanosensitivity in eukaryotic ion channels.…”

Section: Significancementioning

confidence: 99%

Asymmetric mechanosensitivity in a eukaryotic ion channel

Clausen

Jarerattanachat

Carpenter

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Living organisms perceive and respond to a diverse range of mechanical stimuli. A variety of mechanosensitive ion channels have evolved to facilitate these responses, but the molecular mechanisms underlying their exquisite sensitivity to different forces within the membrane remains unclear. TREK-2 is a mammalian twopore domain (K2P) K + channel important for mechanosensation, and recent studies have shown how increased membrane tension favors a more expanded conformation of the channel within the membrane. These channels respond to a complex range of mechanical stimuli, however, and it is uncertain how differences in tension between the inner and outer leaflets of the membrane contribute to this process. To examine this, we have combined computational approaches with functional studies of oppositely oriented single channels within the same lipid bilayer. Our results reveal how the asymmetric structure of TREK-2 allows it to distinguish a broad profile of forces within the membrane, and illustrate the mechanisms that eukaryotic mechanosensitive ion channels may use to detect and fine-tune their responses to different mechanical stimuli.any forms of sensory perception in higher organisms depend on the rapid conversion of mechanical and physical stimuli into the electrochemical language of nerve and muscle cells (1). These transduction mechanisms often involve "mechanosensitive" (MS) ion channels that are able to rapidly convert physicomechanical stimuli into the electrical signals required for complex physiological responses (e.g., touch, pain, hearing, proprioception), as well those mechanical signals that play key roles in development and cell-cell communication (2). The enormous complexity and diversity of these sensory responses suggests that a variety of molecular mechanisms are likely responsible; for example, while some channels are regulated via physical coupling to proteins of the cytoskeleton and/or cell matrix, others respond directly to changes in lipid membrane tension (3). The precise structural and physical mechanisms underlying these processes remain poorly understood, however (4-6).Our current understanding of how membrane tension directly regulates ion channel gating is largely derived from studies of prokaryotic MS ion channels involved in the control of bacterial turgor pressure (7,8). The open state of these MS channels has a larger cross-sectional area than the closed state within the membrane, and stretch-induced changes in the forces within the bilayer stabilize the expanded open-state conformation. This is commonly referred to as the force-from-lipid principle of mechanosensitivity (9). Similar physical principles are thought to regulate many eukaryotic MS channels (5, 10).Typically, the functional activity of MS ion channels is examined in pipette-based patch-clamp recordings in which negative or positive pressures are used to alter bilayer tension. These pressure changes stretch the membrane to alter the lateral pressure profile, the complex profile of forces that vary with location acro...

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Mechanoprotection by Polycystins against Apoptosis Is Mediated through the Opening of Stretch-Activated K2P Channels

Cited by 50 publications

References 66 publications

Mechanically Activated Ion Channels

Mechanically Activated Ion Channels

Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells

Asymmetric mechanosensitivity in a eukaryotic ion channel

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