The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size
The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size
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DOI：
10.1038/ncomms7048
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发表时间：
2015-01-01
影响因子：
16.6
通讯作者：
Gregorevic, P.
中科院分区：
文献类型：
--
作者：
Watt, K. I.;Turner, B. J.;Gregorevic, P.
Yes相关蛋白（雅普）是Hippo通路的核心效应子，其调节器官发育中的增殖和凋亡。雅普功能在上皮细胞和组织中已被广泛表征，但其在成人骨骼肌中的功能仍不清楚。在这里，我们表明，雅普积极调节基础骨骼肌质量和蛋白质合成。从机制上讲，我们发现雅普通过与TEAD转录因子的相互作用调节肌肉质量。此外，肌肉中的雅普丰度和活性在运动神经损伤或变性后增加，作为减轻神经源性肌肉萎缩的过程。我们的研究结果强调了雅普作为骨骼肌大小的正调节剂的重要作用。对促进骨骼肌中雅普活性的干预措施的进一步研究可能有助于开发对抗肌肉萎缩和神经肌肉疾病的治疗方法。
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.