YAP and TAZ regulate cell volume

Area of Science:

• Cell Biology
• Mechanobiology
• Molecular Biology

Background:

• Mammalian cell size regulation is poorly understood, hindered by challenges in high-throughput volume quantification.
• The precise mechanisms by which cells control their physical dimensions remain elusive.

Purpose of the Study:

• To investigate the role of mechanosensitive transcriptional regulators YAP and TAZ in mammalian cell volume regulation.
• To elucidate the pathways and mechanisms through which YAP/TAZ influences cell size.

Main Methods:

• Utilized the fluorescence exclusion method for high-throughput cell volume quantification.
• Investigated the impact of YAP/TAZ on cell cycle duration, cell shape, and cell division volume.
• Assessed the independence of YAP/TAZ-mediated volume regulation from mTOR signaling.
• Examined the role of YAP in regulating intracellular cytoplasmic pressure.
• Studied the effect of inhibiting myosin assembly and cell tension on cell cycle progression.

Main Results:

• Identified YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) as regulators of single-cell volume.
• Demonstrated that YAP/TAZ's role in volume regulation extends beyond cell cycle duration or shape.
• Found YAP/TAZ-mediated volume regulation to be independent of mTOR under experimental conditions.
• Showed that YAP/TAZ directly impacts cell division volume, with YAP regulating intracellular cytoplasmic pressure.
• Inhibiting myosin assembly and cell tension slowed G1 to S phase cell cycle progression, suggesting YAP/TAZ modulates volume with cytoskeletal tension.

Conclusions:

• YAP and TAZ are critical regulators of mammalian cell volume, acting through mechanisms beyond cell cycle control or shape.
• Cellular volume regulation by YAP/TAZ is independent of mTOR signaling.
• YAP/TAZ directly influences cell division volume and intracellular pressure, potentially integrating cytoskeletal tension signals.
• These findings provide new insights into the mechanobiology of cell size control and cell cycle progression.