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Nat Commun ; 6: 6048, 2015 Jan 12.
Article in English | MEDLINE | ID: mdl-25581281

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.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Phosphoproteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Adaptor Proteins, Signal Transducing/genetics , Animals , Blotting, Western , Cell Cycle Proteins , Denervation , Female , HEK293 Cells , Hippo Signaling Pathway , Humans , Hypertrophy , Male , Mice, Inbred C57BL , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Nerve Degeneration/pathology , Organ Size , Phosphoproteins/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factors/metabolism , Up-Regulation , YAP-Signaling Proteins
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