Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2 DOI Creative Commons
Clément Verkest,

Irina Schaefer,

Timo A. Nees

et al.

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

Published: March 15, 2022

A central question in mechanobiology is how mechanical forces acting or on cells are transmitted to mechanically-gated PIEZO channels that convert these into biochemical signals. Here we examined the role of intracellular domains PIEZO2, which account for 25% channel, and demonstrate fine-tune properties such as poking stretch-sensitivity, velocity coding single channel conductance. Moreover, show intrinsically disordered linker between transmembrane helices twelve thirteen (IDR5) required activation PIEZO2 by cytoskeleton-transmitted forces. The deletion IDR5 abolishes PIEZO2-mediated inhibition neurite outgrowth, while it only partially affected its sensitivity cell indentation does not alter stretch sensitivity. Thus, propose a polymodal mechanosensor detects different types stimuli via force transmission pathways, highlights importance utilizing multiple complementary assays when investigating function.

Language: Английский

Discoveries in structure and physiology of mechanically activated ion channels DOI
Jennifer M. Kefauver, Andrew B. Ward, Ardem Patapoutian

et al.

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

Published: Nov. 25, 2020

Language: Английский

Citations

457
Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing DOI Creative Commons
Hamza Atcha, Amit Jairaman, Jesse R. Holt

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 31, 2021

Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine role mechanically activated cation channel Piezo1 in polarization sensing microenvironmental stiffness. We show that macrophages lacking exhibit reduced inflammation enhanced wound healing responses. Additionally, expressing transgenic Ca2+ reporter, Salsa6f, reveal influx is dependent on Piezo1, modulated soluble signals, stiff substrates. Furthermore, stiffness-dependent changes function, both vitro response subcutaneous implantation biomaterials vivo, require Piezo1. Finally, positive feedback between actin drives activation. Together, our studies a mechanosensor stiffness macrophages, its activity modulates

Language: Английский

Citations

332
Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms DOI Open Access
Peng Jin, Lily Yeh Jan, Yuh Nung Jan

et al.

Annual Review of Neuroscience, Journal Year: 2020, Volume and Issue: 43(1), P. 207 - 229

Published: Feb. 22, 2020

Activation of mechanosensitive ion channels underlies a variety fundamental physiological processes that require sensation mechanical force. Different adapt distinctive structures and mechanotransduction mechanisms to fit their biological roles. How work, especially in animals, has been extensively studied the past decade. Here we review key findings functional structural characterizations these highlight features relevant mechanism each specific channel.

Language: Английский

Citations

210
Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis DOI Creative Commons
Whasil Lee, Robert J. Nims, Alireza Savadipour

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(13)

Published: March 23, 2021

Significance Osteoarthritis is a global health problem that affects load-bearing joints, causing loss of mobility and enormous healthcare costs. However, disease-modifying approaches are lacking. Here, we report cellular mechanism inflammatory signaling in chondrocytes, the component cartilage. We show how osteoarthritis-relevant levels interleukin-1α reprogram articular chondrocytes so they become more susceptible to mechanical trauma, which sense via Piezo1/2-mechanosensitive ion channels. uncover IL-1α enhances gene expression P iezo 1 primary underlying Piezo1 enhanced function. elucidate from membrane nucleus, including transcription factors enhance expression. also define consequences increased Piezo1, for mechanotransduction at rest, implicate this reprogramming osteoarthritis pathogenesis.

Language: Английский

Citations

169
Tethering Piezo channels to the actin cytoskeleton for mechanogating via the cadherin-β-catenin mechanotransduction complex DOI Creative Commons
Jing Wang, Jinghui Jiang, Xu-Zhong Yang

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(6), P. 110342 - 110342

Published: Feb. 1, 2022

The mechanically activated Piezo channel plays a versatile role in conferring mechanosensitivity to various cell types. However, how it incorporates its intrinsic and cellular components effectively sense long-range mechanical perturbation across remains elusive. Here we show that channels are biochemically functionally tethered the actin cytoskeleton via cadherin-β-catenin mechanotransduction complex, whose significantly impairs Piezo-mediated responses. Mechanistically, adhesive extracellular domain of E-cadherin interacts with cap Piezo1, which controls transmembrane gate, while cytosolic tail might interact domains close proximity intracellular gates, allowing direct focus adhesion-cytoskeleton-transmitted force for gating. Specific disruption intermolecular interactions prevents cytoskeleton-dependent gating Piezo1. Thus, propose force-from-filament model complement previously suggested force-from-lipids mechanogating channels, enabling them serve as tunable mechanotransducers.

Language: Английский

Citations

150
Fibroblast and myofibroblast activation in normal tissue repair and fibrosis DOI
Fereshteh S. Younesi, Andrew Miller, Thomas H. Barker

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 617 - 638

Published: April 8, 2024

Language: Английский

Citations

143
Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels DOI
Yan Jiang, Xu-Zhong Yang, Jinghui Jiang

et al.

Trends in Biochemical Sciences, Journal Year: 2021, Volume and Issue: 46(6), P. 472 - 488

Published: Feb. 18, 2021

Language: Английский

Citations

132
Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing DOI Creative Commons
Jesse R. Holt, Wei-Zheng Zeng, Elizabeth L. Evans

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Sept. 27, 2021

Keratinocytes, the predominant cell type of epidermis, migrate to reinstate epithelial barrier during wound healing. Mechanical cues are known regulate keratinocyte re-epithelialization and healing; however, underlying molecular transducers biophysical mechanisms remain elusive. Here, we show through molecular, cellular, organismal studies that mechanically activated ion channel PIEZO1 regulates migration Epidermal-specific Piezo1 knockout mice exhibited faster closure while gain-of-function displayed slower compared littermate controls. By imaging spatiotemporal localization dynamics endogenous channels, find enrichment at some regions edge induces a localized cellular retraction slows collective migration. In migrating single keratinocytes, is enriched rear cell, where maximal occurs, chemical activation enhances as well Our findings uncover novel may suggest potential pharmacological target for treatment. More broadly, nanoscale channels can control tissue-scale events, finding with implications beyond healing processes diverse development, homeostasis, disease, repair.

Language: Английский

Citations

113
Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions DOI Creative Commons
Shaopeng Chi, Yaxiong Cui,

Haiping Wang

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(18), P. 2984 - 2999.e8

Published: Aug. 12, 2022

Language: Английский

Citations

98
Force- and cell state–dependent recruitment of Piezo1 drives focal adhesion dynamics and calcium entry DOI Creative Commons
Mingxi Yao, Ajay Tijore, Delfine Cheng

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(45)

Published: Nov. 9, 2022

Mechanosensing is an integral part of many physiological processes including stem cell differentiation, fibrosis, and cancer progression. Two major mechanosensing systems-focal adhesions mechanosensitive ion channels-can convert mechanical features the microenvironment into biochemical signals. We report here unexpectedly that calcium-permeable channel Piezo1, previously perceived to be diffusive on plasma membranes, binds matrix in a force-dependent manner, promoting spreading, adhesion dynamics, calcium entry normal but not most cells tested except some glioblastoma lines. A linker domain Piezo1 needed for binding adhesions, overexpression blocks decreasing size spread area. Thus, we suggest unidentified component focal nontransformed catalyzes maturation growth through signaling, this function absent cells.

Language: Английский

Citations

88