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The Hippo pathway drives the cellular response to hydrostatic pressure
Jiwon Park1,2, Siyang Jia1,2, Donald Salter3
1Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh bioQuarter, The University of Edinburgh, Edinburgh, UK.
The EMBO Journal
|June 15, 2022
Summary
Cells rapidly adjust volume to hydrostatic pressure via YAP/TAZ proteins, influencing cell tension and matrix remodeling. This response ensures cellular homeostasis and plasticity under mechanical stress.
Area of Science:
- Cell Biology
- Mechanobiology
- Biophysics
Background:
- Cells dynamically respond to mechanical and chemical cues for homeostasis and plasticity.
- Cellular responses to elevated interstitial fluid pressure are not well understood.
- Extracellular hydrostatic pressure is a critical mechanical stimulus.
Purpose of the Study:
- To analyze the temporal cellular response to hydrostatic pressure.
- To investigate the role of YAP and TAZ in mediating cellular responses to hydrostatic pressure.
- To elucidate the molecular mechanisms underlying cell volume regulation under hydrostatic pressure.
Main Methods:
- Quantitative label-free digital holographic imaging.
- Genome editing techniques.
- Biochemical assays and confocal imaging.
Main Results:
- Elevated cyclic hydrostatic pressure induces rapid, reversible cell volume changes.
- YAP and TAZ control cell volume and plasma membrane tension.
- YAP/TAZ activation drives hydrostatic pressure response via clathrin-dependent endocytosis.
- Oscillating hydrostatic pressure activates YAP/TAZ, inducing TEAD-mediated transcription.
Conclusions:
- YAP/TAZ are key regulators of cellular response to hydrostatic pressure.
- Clathrin-dependent endocytosis is involved in mediating this response.
- Hydrostatic pressure activates a feedback loop for robust cellular adaptation and extracellular matrix regulation.
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