title: The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size.
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.
authors.affiliation: 1] Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia [2] Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria 3002, Australia.
authors.forename: K I
authors.initials: KI
authors.lastname: Watt
authors.affiliation: The Florey Institute of Neuroscience and Medical Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Turner
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Hagg
authors.affiliation: 1] Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria 3002, Australia [2] Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria 3010, Australia [3] Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Davey
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Qian
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: C E
authors.initials: CE
authors.lastname: Winbanks
authors.affiliation: 1] Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria 3002, Australia [2] Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria 3010, Australia [3] Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: K F
authors.initials: KF
authors.lastname: Harvey
authors.affiliation: 1] Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia [2] Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria 3800, Australia [3] Department of Physiology, The University of Melbourne, Melbourne, Victoria 3010, Australia [4] Department of Neurology, The University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gregorevic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D003714:Denervation; D005260:Female; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology; D009929:Organ Size; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases