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
Permalink -

https://acuresearchbank.acu.edu.au/item/8v89v/phosphoproteomics-reveals-conserved-exercise-stimulated-signaling-and-ampk-regulation-of-store-operated-calcium-entry

Restricted files

Publisher's version

  • 82
    total views
  • 0
    total downloads
  • 2
    views this month
  • 0
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Exercise-regulated mitochondrial and nuclear signalling networks in skeletal muscle
Reisman, Elizabeth G., Hawley, John A. and Hoffman, Nolan J.. (2024). Exercise-regulated mitochondrial and nuclear signalling networks in skeletal muscle. Sports Medicine. 54, pp. 1097-1119. https://doi.org/10.1007/s40279-024-02007-2
Discordant skeletal muscle gene and protein responses to exercise
Bishop, David J., Hoffman, Nolan J., Taylor, Dale F., Saner, Nicholas J., Lee, Matthew J.-C. and Hawley, John A.. (2023). Discordant skeletal muscle gene and protein responses to exercise. Trends in Biochemical Sciences. 48(11), pp. 927-936. https://doi.org/10.1016/j.tibs.2023.08.005
Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator
Ovens, Ashley J., Gee, Yi Sing, Ling, Naomi X. Y., Yu, Dingyi, Hardee, Justin P., Chung, Jin D., Ngoei, Kevin R. W., Waters, Nicholas J., Hoffman, Nolan J., Scott, John W., Loh, Kim, Spengler, Katrin, Heller, Regine, Parker, Michael W., Lynch, Gordon S., Huang, Fei, Galic, Sandra, Kemp, Bruce E., Baell, Jonathan B., ... Langendorf, Christopher G.. (2022). Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator. Biochemical Journal. 479(11), pp. 1181-1204. https://doi.org/10.1042/BCJ20220067
Disrupting AMPK-glycogen binding in mice increases carbohydrate utilization and reduces exercise capacity
Janzen, Natalie R., Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J.. (2022). Disrupting AMPK-glycogen binding in mice increases carbohydrate utilization and reduces exercise capacity. Frontiers in Physiology. 13, p. 859246. https://doi.org/10.3389/fphys.2022.859246
Metabolomics reveals mouse plasma metabolite responses to acute exercise and effects of disrupting AMPK-glycogen interactions
Belhaj, Mehdi, Lawler, Nathan, Hawley, John Alan, Broadhurst, David, Hoffman, Nolan John and Reinke, Stacey. (2022). Metabolomics reveals mouse plasma metabolite responses to acute exercise and effects of disrupting AMPK-glycogen interactions. Frontiers in Molecular Biosciences. pp. 1-16. https://doi.org/10.3389/fmolb.2022.957549
Metabolomics and lipidomics : Expanding the molecular landscape of exercise biology
Belhaj, Mehdi R., Lawler, Nathan G. and Hoffman, Nolan J.. (2021). Metabolomics and lipidomics : Expanding the molecular landscape of exercise biology. Metabolites. 11(151), p. Article 151. https://doi.org/10.3390/metabo11030151
Mice with whole-body disruption of AMPK-glycogen binding have increased adiposity, reduced fat oxidation and altered tissue glycogen dynamics
Janzen, Natalie, Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J.. (2021). Mice with whole-body disruption of AMPK-glycogen binding have increased adiposity, reduced fat oxidation and altered tissue glycogen dynamics. International Journal of Molecular Sciences. 22(17), p. Article: 9616. https://doi.org/10.3390/ijms22179616
PhosR enables processing and functional analysis of phosphoproteomic data
Kim, Hani Jieun, Kim, Taiyun, Hoffman, Nolan J., Xiao, Di, James, David E., Humphrey, Sean J. and Yang, Pengyi. (2021). PhosR enables processing and functional analysis of phosphoproteomic data. Cell Reports. 34, p. 108771. https://doi.org/10.1101/2020.08.31.276329
Omega-3 polyunsaturated fatty acids mitigate palmitate-induced impairments in skeletal muscle cell viability and differentiation
Tachtsis, Bill, Whitfield, Jamie, Hawley, John A. and Hoffman, Nolan J.. (2020). Omega-3 polyunsaturated fatty acids mitigate palmitate-induced impairments in skeletal muscle cell viability and differentiation. Frontiers in Physiology. 11, pp. 1-13. https://doi.org/10.3389/fphys.2020.00563
Genetic loss of AMPK-glycogen binding destabilizes AMPK and disrupts metabolism
Hoffman, Nolan J., Whitfield, Jamie, Janzen, Natalie R., Belhaj, Mehdi R., Galic, Sandra, Murray-Segal, Lisa, Smiles, William J., Ling, Naomi X. Y., Dite, Toby A., Scott, John W., Oakhill, Jonathan S., Brink, Robert, Kemp, Bruce E. and Hawley, John A.. (2020). Genetic loss of AMPK-glycogen binding destabilizes AMPK and disrupts metabolism. Molecular Metabolism. 41, pp. 1-13. https://doi.org/10.1016/j.molmet.2020.101048
High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice
Burchfield, James G., Kebede, Melkam A., Meoli, Christopher C., Stockli, Jacqueline, Whitworth, P. Tess, Wright, Amanda L., Hoffman, Nolan John, Minard, Annabel Y., Ma, Xiuquan, Krycer, James R., Nelson, Marin E., Tan, Shi-Xlong, Yau, Belinda, Thomas, Kristen C., Wee, Natalie K.Y., Khor, Ee-Cheng, Enriquez, Ronaldo F., Vissel, Bryce, Biden, Trevor J., ... Fazakerley, Daniel J.. (2018). High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. Journal of Biological Chemistry. 293(15), pp. 5731 - 5745. https://doi.org/10.1074/jbc.RA117.000808
Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance
Fazakerley, Daniel J., Chaudhuri, Rima, Yang, Pengyi, Maghzal, Ghassan J., Thomas, Kristen C., Krycer, James R., Humphrey, Sean J., Parker, Benjamin, Fisher-Wellman, Kelsey H., Meoli, Christopher C., Hoffman, Nolan, Diskin, Ciana, Burchfield, James G., Cowley, Mark J., Kaplan, Warren, Modrusan, Zora, Kolumam, Ganesh, Yang, Jean Y. H., Chen, Daniel L., ... James, David E.. (2018). Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. eLife. 7, pp. 1 - 38. https://doi.org/10.7554/eLife.32111
Interactive roles for AMPK and glycogen from cellular energy sensing to exercise metabolism
Janzen, Natalie, Whitfield, Jamie and Hoffman, Nolan. (2018). Interactive roles for AMPK and glycogen from cellular energy sensing to exercise metabolism. International Journal of Molecular Sciences. 19(11), pp. 1 - 18. https://doi.org/10.3390/ijms19113344
High dietary fat intake increases fat oxidation and reduces skeletal muscle mitochondrial respiration in trained humans
Leckey, Jill J., Hoffman, Nolan J., Parr, Evelyn B., Devlin, Brooke L., Trewin, Adam J., Stepto, Nigel K., Morton, James P., Burke, Louise M. and Hawley, John A.. (2018). High dietary fat intake increases fat oxidation and reduces skeletal muscle mitochondrial respiration in trained humans. FASEB Journal. 32(6), pp. 2979-2991. https://doi.org/10.1096/fj.201700993R
Metabolomic analysis of insulin resistance across different mouse strains and diets
Stockli, Jacqueline, Fisher-Wellman, Kelsey H., Chaudhuri, Rima, Zeng, Xiao-Yi, Fazakerley, Daniel J., Meoli, Christopher C., Thomas, Kristen C., Hoffman, Nolan, Mangiafico, Salvatore P., Xirouchaki, Chrysovalantou E., Yang, Chieh H., Ilkayeva, Olga, Wong, Kari, Cooney, Gregory J., Andrikopoulos, Sofianos, Muoio, Deborah M. and James, David E.. (2017). Metabolomic analysis of insulin resistance across different mouse strains and diets. Journal of Biological Chemistry. 292(47), pp. 19135 - 19145. https://doi.org/10.1074/jbc.M117.818351
The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs
Dite, Toby A., Ling, Naomi, Scott, John W., Hoque, Ashfaqul, Galic, Sandra, Parker, Benjamin L., Ngoei, Kevin R.W., Langendorf, Christopher G., O'Brien, Matthew, Kundu, Mondira, Viollet, Benoit, Steinberg, Gregory R., Sakamoto, Kei, Kemp, Bruce and Oakhill, Jonathan S.. (2017). The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. Nature Communications. 8(571), pp. 1 - 14. https://doi.org/10.1038/s41467-017-00628-y
Omics and exercise : Global approaches for mapping exercise biological networks
Hoffman, Nolan John. (2017). Omics and exercise : Global approaches for mapping exercise biological networks. Cold Spring Harbor Perspectives in Medicine. 7(10), pp. 1-17. https://doi.org/10.1101/cshperspect.a029884
mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3
Kleinert, Maximilian, Parker, Benjamin L., Chaudhuri, Rima, Fazakerley, Daniel J., Serup, Annette, Thomas, Kristen C., Krycer, James R., Sylow, Lykke, Fritzen, Andreas M., Hoffman, Nolan John, Jeppesen, Jacob, Schjerling, Peter, Ruegg, Markus A., Kiens, Bente, James, David E. and Richter, Erik A.. (2016). mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. Molecular Metabolism. 5(8), pp. 646 - 655. https://doi.org/10.1016/j.molmet.2016.06.007
Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle
Lee-Young, Robert S., Hoffman, Nolan John, Murphy, Kate T., Henstridge, Darren C., Samocha-Bonet, Dorit, Siebel, Andrew L., Iliades, Peter, Zivanovic, Borivoj, Hong, Yet H., Colgan, Timothy D., Kraakman, Michael J., Bruce, Clinton R., Gregorevic, Paul, McConell, Glenn K., Lynch, Gordon S., Drummond, Grant R., Kingwell, Bronwyn A., Greenfield, Jerry R. and Febbraio, Mark A.. (2016). Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle. Molecular Metabolism. 5(11), pp. 1083 - 1091. https://doi.org/10.1016/j.molmet.2016.09.002
Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates
Hoffman, Nolan John, Parker, Benjamin L., Chaudhuri, Rima, Fisher-Wellman, Kelsey H., Kleinert, Maximilian, Humphrey, Sean J., Yang, Pengyi, Holliday, Mira, Trefely, Sophie, Fazakerley, Daniel J., Stöckli, Jacqueline, Burchfield, James G., Jensen, Thomas E., Jothi, Raja, Kiens, Bente, Wojtaszewski, Jørgen F. P., Richter, Erik A. and James, David E.. (2015). Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. Cell Metabolism. 22(5), pp. 922 - 935. https://doi.org/10.1016/j.cmet.2015.09.001
Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells
Rogers, Samuel, McLoy, Rachel A., Parker, Benjamin L., Chaudhuri, Rima, Gayevskiy, Velimir, Hoffman, Nolan John, Watkins, D. Neil, Daly, Roger J., James, David E. and Burgess, Andrew. (2015). Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells. Data in Brief. 5, pp. 45 - 52. https://doi.org/10.1016/j.dib.2015.08.010
The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle
Stockli, Jacqueline, Meoli, Christopher C., Hoffman, Nolan John, Fazakerley, Daniel J., Pant, Himani, Cleasby, Mark E., Ma, Xiuquan, Kleinert, Maximilian, Brandon, Amanda E., Lopez, Jamie A., Cooney, Gregory J. and James, David E.. (2015). The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle. Diabetes. 64(6), pp. 1914 - 1922. https://doi.org/10.2337/db13-1489
Global phosphoproteomic mapping of early mitotic exit in human cells identifies novel substrate dephosphorylation motifs
McLoy, Rachael A., Parker, Benjamin L., Rogers, Samuel, Chaudhuri, Rima, Gayevskiy, Velimir, Hoffman, Nolan John, Ali, Naveid, Watkins, D. Neil, Daly, Roger J., James, David E., Lorca, Thierry, Castro, Anna and Burgess, Andrew. (2015). Global phosphoproteomic mapping of early mitotic exit in human cells identifies novel substrate dephosphorylation motifs. Molecular and Cellular Proteomics. 14(8), pp. 2194 - 2212. https://doi.org/10.1074/mcp.M114.046938
PhosphOrtholog: A web-based tool for cross-species mapping of orthologous protein post-translational modifications
Chaudhuri, Rima, Sadrieh, Arash, Hoffman, Nolan J., Parker, Benjamin L., Humphrey, Sean J., Stockli, Jacqueline, Hill, Adam P., James, David E. and Yang, Jean Yee Hwa. (2015). PhosphOrtholog: A web-based tool for cross-species mapping of orthologous protein post-translational modifications. BMC Genomics. 16(617), pp. 1 - 14. https://doi.org/10.1186/s12864-015-1820-x
Structural basis for phosphorylation and lysine acetylation cross-talk in a kinase motif associated with myocardial ischemia and cardioprotection
Parker, Benjamin L., Shepherd, Nicholas E., Trefely, Sophie, Hoffman, Nolan John, White, Melanie Y., Engholm-Keller, Kasper, Hambly, Brett D., Larsen, Martin R., James, David E. and Cordwell, Stuart J.. (2014). Structural basis for phosphorylation and lysine acetylation cross-talk in a kinase motif associated with myocardial ischemia and cardioprotection. Journal of Biological Chemistry. 289(37), pp. 25890 - 25906. https://doi.org/10.1074/jbc.M114.556035
Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4 plasma membrane translocation
Mokbel, Nancy, Hoffman, Nolan John, Girgis, Christian M., Small, Lewin, Turner, Nigel, Daly, Roger J., Cooney, Gregory J. and Holt, Lowenna J.. (2014). Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4 plasma membrane translocation. Journal of Cellular Physiology. 229(11), pp. 1753 - 1764. https://doi.org/10.1002/jcp.24628
Structural basis for phosphorylation and lysine acetylation crosstalk in a kinase motif associated with myocardial ischemia and cardioprotection
Parker, Benjamin L., Shepherd, Nicholas E., Trefely, Sophie, Hoffman, Nolan John, White, Melanie Y., Engholm-Keller, Kasper, Hambly, Brett D., Larsen, Martin R., James, David E. and Cordwell, Stuart J.. (2014). Structural basis for phosphorylation and lysine acetylation crosstalk in a kinase motif associated with myocardial ischemia and cardioprotection. Journal of Biological Chemistry. 289(37), pp. 25890 - 25906. https://doi.org/10.1074/jbc.M114.556035
Transient silencing of a type IV P-type ATpase results in decreased GLUT4 translocation and altered signaling of MAPK and PI3K pathways
Hurst, Sarah, Hoffman, Nolan, Elmendorf, Jeffrey and Dhar, Madhu. (2014). Transient silencing of a type IV P-type ATpase results in decreased GLUT4 translocation and altered signaling of MAPK and PI3K pathways. In Obesity Epidemic pp. 1 - 21 CreateSpace Independent Publishing Platform.
Chromium enhances insulin responsiveness via AMPK
Hoffman, Nolan John, Penque, Brent A., Habegger, Kirk M., Sealls, Whitney, Tackett, Lixuan and Elmendorf, Jeffrey S.. (2014). Chromium enhances insulin responsiveness via AMPK. Journal of Nutritional Biochemistry. 25(5), pp. 565 - 572. https://doi.org/10.1016/j.jnutbio.2014.01.007
Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to those caused by palmitate treatment
Frangioudakis, Georgia, Diakanastasis, Barbara, Liao, Bing-Qing M., Saville, Jennifer T., Hoffman, Nolan John, Mitchell, Todd W. and Schmitz-Peiffer, Carsten. (2013). Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to those caused by palmitate treatment. Diabetologia. 56(12), pp. 2697 - 2701. https://doi.org/10.1007/s00125-013-3035-5
AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol
Hoffman, Nolan John, Habegger, Kirk M., Ridenour, Colin M., Broznick, Joseph T. and Elmendon, Jeffrey S.. (2012). AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol. Endocrinology. 153(5), pp. 2130 - 2141. https://doi.org/10.1210/en.2011-2099
Signaling, cytoskeletal and membrane mechanisms regulating GLUT4 exocytosis
Hoffman, Nolan John and Elmendorf, Jeffrey S.. (2011). Signaling, cytoskeletal and membrane mechanisms regulating GLUT4 exocytosis. Trends in Endocrinology and Metabolism. 22(3), pp. 110 - 116. https://doi.org/10.1016/j.tem.2010.12.001