Mechanosensor Piezo1 mediates bimodal patterns of intracellular calcium and FAK signaling
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 17, 2022
- Source ID
- 10.15252/embj.2022111799
Entities
People
- Chi Woo Yoon
- Christopher Carmona
- Daryl Preece
- Linda Zhixia Shi
- Longwei Liu
- Michael W. Berns
- Seung‐hyun Woo
- Shaoying Lu
- Shu Chien
- Veronica Gomez‐godinez
- Yijia Pan
- Yingxiao Wang
Organizations
- Air Force Office of Scientific Research
- National Institutes of Health
- National Science Foundation
- Scripps Research
- University of California
- University of California, San Diego