Journal article

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

KI Watt, BJ Turner, A Hagg, X Zhang, JR Davey, H Qian, C Beyer, CE Winbanks, KF Harvey, P Gregorevic

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2015

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 ..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHMRC


Funding Acknowledgements

We thank Dr Rachel Thomson for technical assistance and Dr Iska Carmichael, Monash Micro Imaging facility, AMREP campus, BakerIDI. This work was supported by Project Grant funding (1009995 awarded to P.G. and K.F.H., 1008910 awarded to B.J.T.) from the Australian National Health and Medical Research Council (NHMRC). K.F.H. is a Sylvia and Charles Viertel Senior Medical Research Fellow. P.G. is supported by a Career Development Fellowship (1046782) from the NHMRC, and was previously supported by a Senior Research Fellowship, sponsored by Pfizer Australia. B.J.T. is supported by the Susie Harris Memorial Fund, MND research grant, MND Research Institute of Australia. The Baker IDI Heart and Diabetes Institute and The Florey Institute of Neuroscience and Medical health are supported in part by the Operational Infrastructure Support Program of the Victorian Government.