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

被引:125
作者
Watt, K. I. [1 ,2 ]
Turner, B. J. [3 ]
Hagg, A. [1 ]
Zhang, X. [2 ,4 ]
Davey, J. R. [1 ]
Qian, H. [1 ]
Beyer, C. [1 ]
Winbanks, C. E. [1 ]
Harvey, K. F. [2 ,4 ,5 ]
Gregorevic, P. [1 ,6 ,7 ,8 ]
机构
[1] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia
[2] East Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia
[3] Univ Melbourne, Florey Inst Neurosci & Med Hlth, Melbourne, Vic 3010, Australia
[4] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia
[5] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia
[6] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia
[7] Univ Melbourne, Dept Physiol, Melbourne, Vic 3010, Australia
[8] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
CARDIOMYOCYTE PROLIFERATION; MOLECULAR-MECHANISMS; TISSUE-GROWTH; ORGAN SIZE; TARGET; MECHANOTRANSDUCTION; REGENERATION; COACTIVATOR; YAP/TAZ; MTORC1;
D O I
10.1038/ncomms7048
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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.
引用
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页数:13
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