title: Deep proteomics of mouse skeletal muscle enables quantitation of protein isoforms, metabolic pathways, and transcription factors.
abstract: Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms.
authors.affiliation: From the ‡Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany;
authors.forename: Atul S
authors.initials: AS
authors.lastname: Deshmukh
authors.affiliation: From the ‡Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany; §Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35121 Padua, Italy;
authors.forename: Marta
authors.initials: M
authors.lastname: Murgia
authors.affiliation: From the ‡Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany;
authors.forename: Nagarjuna
authors.initials: N
authors.lastname: Nagaraj
authors.affiliation: ¶The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Treebak
authors.affiliation: From the ‡Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Cox
authors.affiliation: From the ‡Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany; ‖The Novo Nordisk Foundation Center for Protein Research, Department for proteomics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark mmann@biochem.mpg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D007328:Insulin; D020033:Protein Isoforms; D020543:Proteome; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases; D005947:Glucose