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

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作者
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
机构
[1] Baker IDI Heart and Diabetes Institute,Sir Peter MacCallum Department of Oncology
[2] ,Department of Pathology
[3] Peter MacCallum Cancer Centre,Department of Biochemistry and Molecular Biology
[4] East Melbourne,Department of Physiology
[5] The Florey Institute of Neuroscience and Medical Health,Department of Neurology
[6] The University of Melbourne,undefined
[7] The University of Melbourne,undefined
[8] The University of Melbourne,undefined
[9] Monash University,undefined
[10] The University of Melbourne,undefined
[11] The University of Washington School of Medicine,undefined
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Nature Communications | / 6卷
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摘要
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.
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