Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

eLife, Journal Year: 2015, Volume and Issue: 4

Published: Dec. 8, 2015

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent sensitivity varies substantially across cellular environments, stimulating methods protocols, raising fundamental questions what precise physical stimulus activates channel how its is regulated. Here, we measured currents evoked by membrane stretch three patch configurations, while simultaneously visualizing measuring geometry. Building on this approach, developed protocols minimize resting curvature tension prior probing activity. We find that responds lateral with exquisite as compared other mechanically activated can drive inactivation, thereby tuning overall Piezo1. Our results explain function efficiently adaptable a sensor stimulation diverse contexts.

Language: Английский

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OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels

eLife, Journal Year: 2018, Volume and Issue: 7

Published: Nov. 1, 2018

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA have been described in plants animals. Here, we show that various members of the OSCA TMEM63 family proteins from plants, flies, mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate OSCA1.2, one Arabidopsis thaliana proteins, is an inherently mechanosensitive, pore-forming channel. Our results suggest OSCA/TMEM63 largest identified, conserved across eukaryotes. findings will enable studies gain deep insight molecular mechanisms channel gating, facilitate a better understanding mechanosensory processes vivo

Language: Английский

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VRACs and other ion channels and transporters in the regulation of cell volume and beyond

Nature Reviews Molecular Cell Biology, Journal Year: 2016, Volume and Issue: 17(5), P. 293 - 307

Published: April 1, 2016

Language: Английский

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Cell Membranes Resist Flow

Cell, Journal Year: 2018, Volume and Issue: 175(7), P. 1769 - 1779.e13

Published: Nov. 1, 2018

Language: Английский

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Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 25, 2022

Ultrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, biomolecular cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for use this technology research clinical applications. Here, we show that primary murine cortical culture through a primarily mechanical mechanism mediated specific calcium-selective mechanosensitive ion channels. The activation these channels results gradual build-up calcium, is amplified calcium- voltage-gated channels, generating burst firing response. Cavitation, temperature changes, large-scale deformation, synaptic transmission are not required excitation occur. Pharmacological inhibition leads reduced responses ultrasound, while over-expressing stronger ultrasonic stimulation. These findings mechanistic explanation effect on facilitate further development sonogenetics as tools neuroscience research.

Language: Английский

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Tissue mechanics regulate brain development, homeostasis and disease

Journal of Cell Science, Journal Year: 2017, Volume and Issue: 130(1), P. 71 - 82

Published: Jan. 1, 2017

All cells sense and integrate mechanical biochemical cues from their environment to orchestrate organismal development maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby force translated into signals that can influence cell differentiation, survival, proliferation migration change behavior. Not surprisingly, disease develops if these are abnormal or misinterpreted by - for example, when interstitial pressure compression aberrantly increases, extracellular matrix (ECM) abnormally stiffens. Disease might also develop ability of regulate contractility becomes corrupted. Consistently, states, such as cardiovascular disease, fibrosis cancer, characterized dramatic changes in mechanics, dysregulation forces at level activate mechanosignaling compromise integrity function, promote progression. In this Commentary, we discuss impact mechanics on homeostasis focusing role brain development, neural degeneration, well cancer.

Language: Английский

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Deep Sequencing of Somatosensory Neurons Reveals Molecular Determinants of Intrinsic Physiological Properties

Neuron, Journal Year: 2019, Volume and Issue: 103(4), P. 598 - 616.e7

Published: June 24, 2019

Language: Английский

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Advances in understanding nociception and neuropathic pain

Journal of Neurology, Journal Year: 2017, Volume and Issue: 265(2), P. 231 - 238

Published: Oct. 14, 2017

Pain results from the activation of a subset sensory neurones termed nociceptors and has evolved as "detect protect" mechanism. However, lesion or disease in system can result neuropathic pain, which serves no protective function. Understanding how nervous works what changes occur pain are vital identifying new therapeutic targets developing novel analgesics. In recent years, technologies such optogenetics RNA-sequencing have been developed, alongside more traditional use animal models insights genetic variations humans enabled significant advances to be made mechanistic understanding pain.

Language: Английский

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Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(50), P. 12817 - 12822

Published: Nov. 27, 2018

Significance PIEZOs are mechanically activated cation channels. Recently, loss-of-function mutations of human PIEZO1 were found among patients with familial lymphedema, suggesting a requirement in the lymphatic system. In this paper, utilizing mouse models lacking endothelial cells, we show that ion channel is required for formation valves, key structure proper circulation lymph body. The valve provides mechanistic insight on how variants cause dysfunction patients. This study also extends relevance beyond acute signaling molecules (e.g., touch sensation) and highlights importance these channels controlling morphological/structural specification during development.

Language: Английский

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Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection

Cell, Journal Year: 2018, Volume and Issue: 173(2), P. 443 - 455.e12

Published: March 22, 2018

Language: Английский

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