Mechanosensor Piezo1 mediates bimodal patterns of intracellular calcium and FAK signaling

• Published in: The EMBO journal Vol. 41; no. 17; pp. e111799 - n/a
• Main Authors: Pan, Yijia, Shi, Linda Zhixia, Yoon, Chi Woo, Preece, Daryl, Gomez‐Godinez, Veronica, Lu, Shaoying, Carmona, Christopher, Woo, Seung‐Hyun, Chien, Shu, Berns, Michael W, Liu, Longwei, Wang, Yingxiao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2022; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Biosensors; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium Signaling; Calcium signalling; Cations; EMBO20; EMBO37; Energy transfer; FAK; Fluorescence resonance energy transfer; Focal adhesion kinase; Intracellular; Intracellular signalling; Ion channels; Ion Channels - genetics; Ion Channels - metabolism; laser‐induced shockwaves; Ligands; Mechanical stimuli; Mechanotransduction, Cellular - physiology; Piezo1; Shear stress; Shock waves; SHP2; Signaling; Stimulation; FAK; SHP2; calcium; Piezo1; laser‐induced shockwaves; laser-induced shockwaves
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.2022111799

Piezo1 belongs to mechano‐activatable cation channels serving as biological force sensors. However, the molecular events downstream of Piezo1 activation remain unclear. In this study, we used biosensors based on fluorescence resonance energy transfer (FRET) to investigate the dynamic modes of Piezo1‐mediated signaling and revealed a bimodal pattern of Piezo1‐induced intracellular calcium signaling. Laser‐induced shockwaves (LIS) and its associated shear stress can mechanically activate Piezo1 to induce transient intracellular calcium (Ca [i] ) elevation, accompanied by an increase in FAK activity. Interestingly, multiple pulses of shockwave stimulation caused a more sustained calcium increase and a decrease in FAK activity. Similarly, tuning the degree of Piezo1 activation by titrating either the dosage of Piezo1 ligand Yoda1 or the expression level of Piezo1 produced a similar bimodal pattern of FAK responses. Further investigations revealed that SHP2 serves as an intermediate regulator mediating this bimodal pattern in Piezo1 sensing and signaling. These results suggest that the degrees of Piezo1 activation induced by both mechanical LIS and chemical ligand stimulation may determine downstream signaling characteristics. Synopsis How activation of the mechano‐sensitive Piezo1 cation channel transmits signals remains incompletely understood. Here, the degree of Piezo1 activation induced by mechanical force or chemical ligand stimulation is found to determine downstream signaling characteristics. FRET imaging in live cells monitors the effects of laser‐induced shockwaves (LIS) and their associated shear stress, and of Piezo1 stimulation by its chemical ligand Yoda1. Mechanical or chemical activation of Piezo1 induces transient intracellular calcium elevation, accompanied by an increase in FAK activity. Multiple pulses of shockwave stimulation cause a more sustained calcium increase and a decrease in FAK activity. SHP2 can serve as an intermediate regulator mediating this bimodal pattern in Piezo1 sensing and signaling. Graphical Abstract Combination of mechanical laser‐induced shockwave or chemical ligand Yoda1 stimulation and FRET imaging in live cells reveals that transient versus sustained calcium influx through mechano‐activatable channels has opposite effects on FAK kinase activity.