Deep proteomics of mouse skeletal muscle enables quantitation of protein isoforms, metabolic pathways, and transcription factors

Mol Cell Proteomics. 2015 Apr;14(4):841-53. doi: 10.1074/mcp.M114.044222. Epub 2015 Jan 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Aging / metabolism
  • Animals
  • Cell Line
  • Female
  • Glucose / metabolism
  • Insulin / metabolism
  • Metabolic Networks and Pathways*
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / metabolism*
  • Protein Isoforms / metabolism
  • Proteome / metabolism
  • Proteomics / methods*
  • Signal Transduction
  • Transcription Factors / metabolism*

Substances

  • Insulin
  • Protein Isoforms
  • Proteome
  • Transcription Factors
  • AMP-Activated Protein Kinases
  • Glucose