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Substrate rigidity-dependent positive feedback regulation between YAP and ROCK2.

Wataru Sugimoto1, Katsuhiko Itoh1, Yasumasa Mitsui1

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Mechanobiology

Background:

  • Extracellular matrix (ECM) stiffness impacts cellular functions by altering gene expression.
  • ROCK2, involved in cell migration and proliferation, is upregulated by stiff ECM, but the mechanism is unclear.
  • Yes-associated protein (YAP) is a known mechanotransduction regulator.

Purpose of the Study:

  • To elucidate the mechanism by which ECM rigidity regulates ROCK2 expression.
  • To investigate the role of YAP in the rigidity-dependent regulation of ROCK2.
  • To identify potential feedback loops between YAP and ROCK2.

Main Methods:

  • Investigated YAP's interaction with the ROCK2 promoter.
  • Utilized YAP knockdown and constitutively active YAP expression.
  • Assessed ROCK2 promoter activity and YAP transcriptional activity.

Main Results:

  • YAP upregulates ROCK2 expression in an ECM rigidity-dependent manner.
  • YAP directly interacts with the ROCK2 promoter.
  • ROCK2 expression enhances YAP-mediated transcriptional activation.
  • A positive feedback loop between YAP and ROCK2, modulated by ECM stiffness, was identified.

Conclusions:

  • YAP acts as a key mediator linking ECM stiffness to ROCK2 expression.
  • A novel positive feedback loop between YAP and ROCK2 exists, regulated by ECM rigidity.
  • This feedback loop provides a new mechanism for understanding mechanotransduction in cellular processes.