Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry

Research output: Contribution to journalJournal articlepeer-review

  • Marin E Nelson
  • Benjamin L Parker
  • James G Burchfield
  • Nolan J Hoffman
  • Elise J Needham
  • Kristen C Cooke
  • Timur Naim
  • Sylow, Lykke
  • Naomi X Y Ling
  • Deanne Francis
  • Dougall M Norris
  • Rima Chaudhuri
  • Jonathan S Oakhill
  • Richter, Erik A.
  • Gordon S Lynch
  • Jacqueline Stöckli
  • David E James

Exercise stimulates cellular and physiological adaptations that are associated with widespread health benefits. To uncover conserved protein phosphorylation events underlying this adaptive response, we performed mass spectrometry-based phosphoproteomic analyses of skeletal muscle from two widely used rodent models: treadmill running in mice and in situ muscle contraction in rats. We overlaid these phosphoproteomic signatures with cycling in humans to identify common cross-species phosphosite responses, as well as unique model-specific regulation. We identified > 22,000 phosphosites, revealing orthologous protein phosphorylation and overlapping signaling pathways regulated by exercise. This included two conserved phosphosites on stromal interaction molecule 1 (STIM1), which we validate as AMPK substrates. Furthermore, we demonstrate that AMPK-mediated phosphorylation of STIM1 negatively regulates store-operated calcium entry, and this is beneficial for exercise in Drosophila. This integrated cross-species resource of exercise-regulated signaling in human, mouse, and rat skeletal muscle has uncovered conserved networks and unraveled crosstalk between AMPK and intracellular calcium flux.

Original languageEnglish
Article numbere102578
JournalE M B O Journal
Issue number24
Number of pages20
Publication statusPublished - 2019

ID: 225956874