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

Journal article

Nelson, Marin E., Parker, Benjamin L., Burchfield, James G., Hoffman, Nolan J., Needham, Elise J., Cooke, Kristen C., Naim, Timur, Sylow, Lykke, Ling, Naomi X. Y., Francis, Deanne, Norris, Dougall M., Chaudhuri, Rima, Oakhill, Jonathan S., Richter, Erik A., Lynch, Gordon S., Stockli, Jacqueline and James, David E.. (2019). Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry. The EMBO Journal. 38(24), pp. 1 - 20. https://doi.org/10.15252/embj.2019102578
AuthorsNelson, Marin E., Parker, Benjamin L., Burchfield, James G., Hoffman, Nolan J., Needham, Elise J., Cooke, Kristen C., Naim, Timur, Sylow, Lykke, Ling, Naomi X. Y., Francis, Deanne, Norris, Dougall M., Chaudhuri, Rima, Oakhill, Jonathan S., Richter, Erik A., Lynch, Gordon S., Stockli, Jacqueline and James, David E.
Abstract

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.

KeywordsAMPK; calcium; exercise; phosphorylation; STIM1
Year2019
JournalThe EMBO Journal
Journal citation38 (24), pp. 1 - 20
PublisherWiley-Blackwell Publishing Ltd.
ISSN0261-4189
Digital Object Identifier (DOI)https://doi.org/10.15252/embj.2019102578
Scopus EID2-s2.0-85070712049
Page range1 - 20
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationUnited Kingdom
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