Discoveries in structure and physiology of mechanically activated ion channels

Nature, Journal Year: 2020, Volume and Issue: 587(7835), P. 567 - 576

Published: Nov. 25, 2020

Language: Английский

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A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression

Neuron, Journal Year: 2018, Volume and Issue: 100(4), P. 799 - 815.e7

Published: Oct. 18, 2018

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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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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The mechanosensitive Piezo1 channel is required for bone formation

eLife, Journal Year: 2019, Volume and Issue: 8

Published: July 10, 2019

Mechanical load of the skeleton system is essential for development, growth, and maintenance bone. However, molecular mechanism by which mechanical stimuli are converted into osteogenesis bone formation remains unclear. Here we report that Piezo1, a bona fide mechanotransducer critical various biological processes, plays role in formation. Knockout Piezo1 osteoblast lineage cells disrupts osteoblasts severely impairs structure strength. Bone loss induced unloading blunted knockout mice. Intriguingly, simulated microgravity treatment reduced function suppressing expression Piezo1. Furthermore, osteoporosis patients show closely correlated with dysfunction. These data collectively suggest functions as key conferring mechanosensitivity to determining mechanical-load-dependent formation, represents novel therapeutic target treating or unloading-induced severe loss.

Language: Английский

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Force-induced conformational changes in PIEZO1

Nature, Journal Year: 2019, Volume and Issue: 573(7773), P. 230 - 234

Published: Aug. 21, 2019

Language: Английский

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Structure and mechanogating of the mammalian tactile channel PIEZO2

Nature, Journal Year: 2019, Volume and Issue: 573(7773), P. 225 - 229

Published: Aug. 21, 2019

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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A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: April 3, 2018

Abstract Piezo1 represents a prototype of eukaryotic mechanotransduction channels. The full-length 2547-residue mouse possesses unique 38-transmembrane-helix (TM) topology and is organized into three-bladed, propeller-shaped architecture, comprising central ion-conducting pore, three peripheral blade-like structures, 90-Å-long intracellular beam-resembling structures that bridge the blades to pore. However, how mechanical force chemicals activate gigantic machinery remains elusive. Here we identify novel set chemical activators, termed Jedi, which activates through extracellular side blade instead C-terminal domain indicating long-range allosteric gating. Remarkably, Jedi-induced activation requires key components, including two loops in distal leucine residues proximal end beam. Thus, employs blade-beam-constituted lever-like apparatus as designated transduction pathway for long-distance mechano- chemical-gating

Language: Английский

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Dietary fatty acids fine-tune Piezo1 mechanical response

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: March 13, 2019

Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture remodeling, cell migration, erythrocyte volume. identity of the components that modulate function remain largely unknown. Using lipid profiling analyses, we here identify dietary fatty acids tune mechanical response. We find margaric acid, a saturated acid present in dairy products fish, inhibits activation polyunsaturated (PUFAs), fish oils, inactivation. Force measurements reveal increases bending stiffness, whereas PUFAs decrease it. use supplementation abrogate phenotype gain-of-function mutations causing human dehydrated hereditary stomatocytosis. Beyond Piezo1, our findings demonstrate cell-intrinsic profile changes metabolism can dictate cell's response cues.

Language: Английский

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