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YAP and TAZ regulate cell volume.

Nicolas A Perez-Gonzalez1, Nash D Rochman1, Kai Yao2

  • 1Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.

The Journal of Cell Biology
|September 5, 2019
PubMed
Summary
This summary is machine-generated.

Mammalian cell size regulation is clarified by identifying YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) as key regulators. These mechanosensitive proteins directly impact cell division volume and cytoplasmic pressure.

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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.