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The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size

Author

Listed:
  • K. I. Watt

    (Baker IDI Heart and Diabetes Institute,
    Peter MacCallum Cancer Centre, East Melbourne)

  • B. J. Turner

    (The Florey Institute of Neuroscience and Medical Health, The University of Melbourne)

  • A. Hagg

    (Baker IDI Heart and Diabetes Institute,)

  • X. Zhang

    (Peter MacCallum Cancer Centre, East Melbourne
    The University of Melbourne
    The University of Melbourne)

  • J. R. Davey

    (Baker IDI Heart and Diabetes Institute,)

  • H. Qian

    (Baker IDI Heart and Diabetes Institute,)

  • C. Beyer

    (Baker IDI Heart and Diabetes Institute,)

  • C. E. Winbanks

    (Baker IDI Heart and Diabetes Institute,)

  • K. F. Harvey

    (Peter MacCallum Cancer Centre, East Melbourne
    The University of Melbourne
    The University of Melbourne)

  • P. Gregorevic

    (Baker IDI Heart and Diabetes Institute,
    Monash University
    The University of Melbourne
    The University of Washington School of Medicine)

Abstract

The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ development. YAP function has been extensively characterized in epithelial cells and tissues, but its function in adult skeletal muscle remains poorly defined. Here we show that YAP positively regulates basal skeletal muscle mass and protein synthesis. Mechanistically, we show that YAP regulates muscle mass via interaction with TEAD transcription factors. Furthermore, YAP abundance and activity in muscles is increased following injury or degeneration of motor nerves, as a process to mitigate neurogenic muscle atrophy. Our findings highlight an essential role for YAP as a positive regulator of skeletal muscle size. Further investigation of interventions that promote YAP activity in skeletal muscle might aid the development of therapeutics to combat muscle wasting and neuromuscular disorders.

Suggested Citation

  • K. I. Watt & B. J. Turner & A. Hagg & X. Zhang & J. R. Davey & H. Qian & C. Beyer & C. E. Winbanks & K. F. Harvey & P. Gregorevic, 2015. "The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7048
    DOI: 10.1038/ncomms7048
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