Yes-Associated Protein is up-regulated by mechanical overload and is sufficient to induce skeletal muscle hypertrophy

• Published in: FEBS letters 2015-06, Vol.589 (13), p.1491-1497
• Main Authors: Goodman, Craig A., Dietz, Jason M., Jacobs, Brittany L., McNally, Rachel M., You, Jae-Sung, Hornberger, Troy A.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Blotting, Western; BMP4; bone morphogenic protein 4; Cell Cycle Proteins; cross-sectional area; CSA; Female; Gene Expression Regulation; Hippo pathway; Hypertrophy; large tumor suppressor kinases 1 and 2; LATS1/2; Male; Mammalian/mechanistic target of rapamycin complex 1; MCAT; Mechanistic Target of Rapamycin Complex 1; Mechanotransduction; Mice; Microscopy, Fluorescence; mTORC1; Multiprotein Complexes - metabolism; MuRF1; muscle cytosine, adenine and thymine; Muscle Proteins - genetics; muscle ring finger 1; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; MyoD Protein - genetics; Phosphoproteins - genetics; Phosphoproteins - metabolism; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins c-myc - genetics; SBE; Signal Transduction; Smad binding element; Smad2 Protein - metabolism; Smad3 Protein - metabolism; Stress, Mechanical; Synergist ablation; TEA domain; TEAD; TGF-β; Tibialis Anterior; TOR Serine-Threonine Kinases - metabolism; transforming growth factor beta; Tripartite Motif Proteins; ubiquitin proteasome system; Ubiquitin-Protein Ligases - genetics; Up-Regulation; UPS; YAP; YAP-Signaling Proteins; Yes-Associated Protein
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.04.047

•We examined YAP protein expression and mTORC1 activation in overloaded muscles.•We also examined the effect of transient YAP overexpression on muscle fiber size.•Overload-induced increases in YAP and mTORC1 signaling follow different time courses.•YAP overexpression induced mTORC1-independent muscle fiber hypertrophy.•YAP is a novel mTORC1-independent regulator of skeletal muscle mass. Mechanically-induced skeletal muscle growth is regulated by mammalian/mechanistic target of rapamycin complex 1 (mTORC1). Yes-Associated Protein (YAP) is a mechanically-sensitive, and growth-related, transcriptional co-activator that can regulate mTORC1. Here we show that, in skeletal muscle, mechanical overload promotes an increase in YAP expression; however, the time course of YAP expression is markedly different from that of mTORC1 activation. We also show that the overexpression of YAP induces hypertrophy via an mTORC1-independent mechanism. Finally, we provide preliminary evidence of possible mediators of YAP-induced hypertrophy (e.g. increased MyoD and c-Myc expression, and decreased Smad2/3 activity and muscle ring finger 1 (MuRF1) expression).