Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry
Research output: Contribution to journal › Journal article › Research › peer-review
Marin E Nelson, Benjamin L Parker, James G Burchfield, Nolan J Hoffman, Elise J Needham, Kristen C Cooke, Timur Naim, Lykke Sylow, Naomi X Y Ling, Deanne Francis, Dougall M Norris, Rima Chaudhuri, Jonathan S Oakhill, Erik Richter, 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.
|Journal||E M B O Journal|
|Publication status||E-pub ahead of print - 5 Aug 2019|
- The Faculty of Science - AMPK, Calcium, Exercise, Phosphorylation, STIM1