Sphingomyelinase Disables Inactivation in Endogenous PIEZO1 Channels

Shi, Jing; Hyman, Adam J.; Vecchis, Dario De; Chong, Jiehan; Lichtenstein, Laeticia; Futers, T. Simon; Rouahi, Myriam; Negre-Salvayre, Anne; Augé, Nathalie; Kalli, Antreas C.; Beech, David J.

doi:10.1016/j.celrep.2020.108225

Cited by 56 publications

(59 citation statements)

References 63 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sphingomyelin (substrates of SMPD3), unlike ceramide, does not influence inactivation but does influence channel force sensitivities. This indicated sphingomyelinase activities, ceramide, and sphingomyelin as regulators of native Piezo gating, which permits prolong activities [72]. In addition to these outstanding findings, Scheuring and colleagues demonstrated that Piezo1 is a springy structure that normally bends the cellular membrane where it lies, but will flatten out when for instance a mechanical force is applied to the cell membrane.…”

Section: Piezo1 Activation and Inactivation Mechanismsmentioning

confidence: 96%

Emerging Piezo1 signaling in inflammation and atherosclerosis; a potential therapeutic target

Shinge¹,

Zhang²,

Din³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Purpose of Review: Atherosclerosis is the principal cause of cardiovascular diseases (CVDs) which are the major cause of death worldwide. Mechanical force plays an essential role in cardiovascular health and disease. To bring the awareness of mechanosensitive Piezo1 role in atherosclerosis and its therapeutic potentials we review recent literature to highlight its involvement in various mechanisms of the disease. Recent Findings: Recent studies reported Piezo1 channel as a sensor, and transducer of various mechanical forces into biochemical signals, which affect various cellular activities such as proliferation, migration, apoptosis and vascular remodeling including immune/inflammatory mechanisms fundamental phenomenon in atherogenesis. Summary: Numerous evidences suggest Piezo1 as a player in different mechanisms of cell biology, including immune/inflammatory and other cellular mechanisms correlated with atherosclerosis. This review discusses mechanistic insight about this matter and highlights the drugability and therapeutic potentials consistent with emerging functions Piezo1 in various mechanisms of atherosclerosis. Based on the recent works, we suggest Piezo1 as potential therapeutic target and a valid candidate for future research. Therefore, a deeper exploration of Piezo1 biology and translation towards the clinic will be a novel strategy for treating atherosclerosis and other CVDs.

show abstract

Section: Piezo1 Activation and Inactivation Mechanismsmentioning

confidence: 96%

Emerging Piezo1 signaling in inflammation and atherosclerosis; a potential therapeutic target

Shinge¹,

Zhang²,

Din³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…However, heterologous expression of Piezo1 cDNA from mES cells displays fast inactivation kinetics, indicating that additional regulatory mechanisms other than the amino acid sequence determine the slow kinetics of the Piezo1 channel in mES cells [ 70 ]. Recently, sphingomyelinase activity has been revealed to be a crucial determinant of Piezo1 inactivation [ 71 ]. Various modulators, such as pH, temperature, divalent ion concentrations, alternative splicing, osmotic swelling, membrane lipid composition, co-expression of other membrane proteins, and G-protein-coupled pathways have also been reported to regulate the Piezo channel kinetics [ 55 , 72 – 79 ]; however, we still know very little about the relationships among these factors and pivotal structural domains.…”

Section: Kinetics Properties Of Piezo Channelsmentioning

confidence: 99%

Structure, kinetic properties and biological function of mechanosensitive Piezo channels

et al. 2021

View full text Add to dashboard Cite

Mechanotransduction couples mechanical stimulation with ion flux, which is critical for normal biological processes involved in neuronal cell development, pain sensation, and red blood cell volume regulation. Although they are key mechanotransducers, mechanosensitive ion channels in mammals have remained difficult to identify. In 2010, Coste and colleagues revealed a novel family of mechanically activated cation channels in eukaryotes, consisting of Piezo1 and Piezo2 channels. These have been proposed as the long-sought-after mechanosensitive cation channels in mammals. Piezo1 and Piezo2 exhibit a unique propeller-shaped architecture and have been implicated in mechanotransduction in various critical processes, including touch sensation, balance, and cardiovascular regulation. Furthermore, several mutations in Piezo channels have been shown to cause multiple hereditary human disorders, such as autosomal recessive congenital lymphatic dysplasia. Notably, mutations that cause dehydrated hereditary xerocytosis alter the rate of Piezo channel inactivation, indicating the critical role of their kinetics in normal physiology. Given the importance of Piezo channels in understanding the mechanotransduction process, this review focuses on their structural details, kinetic properties and potential function as mechanosensors. We also briefly review the hereditary diseases caused by mutations in Piezo genes, which is key for understanding the function of these proteins.

show abstract

“…PIEZO1 inactivation is affected by the presence of specific lipids 32,33 , metal ions 30 , disease mutations 34 , as well as external pH 35 , membrane potential 36 , and other unknown cellular factors 37 . In addition to this long list, our study shows that the rate of PIEZO1 inactivation accelerates as more channels open in a patch.…”

Section: Discussionmentioning

confidence: 99%

An inter-channel cooperative mechanism mediates PIEZO1’s exquisite mechanosensitivity

Wijerathne

Jiang

et al. 2021

Preprint

View full text Add to dashboard Cite

The bowl-shaped structure of PIEZO channels is predicted to flatten in response to mechanical stimuli, gating their pore open. However, how this unique structure allows them to detect exquisitely small changes in membrane tension remains unclear. Here, using pressure clamp electrophysiology, modeling, and molecular dynamics simulations, we show that the single channel open probability of PIEZO1 increases weakly with respect to pressure-induced tension. In contrast, when multiple channels are present in a membrane patch, channel open probability increases steeply as a function of the number of open channels. These cooperative effects are consistent with an inter-channel energetic repulsion due to the local membrane deformation created by the non-planar PIEZO structure. When channels open, this deformation shrinks, allowing open channels to diffuse closer to each other, thus delaying closure. This study reveals how PIEZO1 channels acquire their exceptional mechanosensitivity.

show abstract

Sphingomyelinase Disables Inactivation in Endogenous PIEZO1 Channels

Cited by 56 publications

References 63 publications

Emerging Piezo1 signaling in inflammation and atherosclerosis; a potential therapeutic target

Emerging Piezo1 signaling in inflammation and atherosclerosis; a potential therapeutic target

Structure, kinetic properties and biological function of mechanosensitive Piezo channels

An inter-channel cooperative mechanism mediates PIEZO1’s exquisite mechanosensitivity

Contact Info

Product

Resources

About