Gene Symbol: Gys1
Description: glycogen synthase 1, muscle
Alias: Gys3, MGS, glycogen [starch] synthase, muscle, glycogen synthase 3, brain
Species: mouse
Products:     Gys1

Top Publications

  1. Fujii N, Boppart M, Dufresne S, Crowley P, Jozsi A, Sakamoto K, et al. Overexpression or ablation of JNK in skeletal muscle has no effect on glycogen synthase activity. Am J Physiol Cell Physiol. 2004;287:C200-8 pubmed
    ..JNK activation is unlikely to be the major mechanism by which contractile activity increases glycogen synthase activity in skeletal muscle. ..
  2. Valles Ortega J, Duran J, Garcia Rocha M, Bosch C, Saez I, Pujadas L, et al. Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease. EMBO Mol Med. 2011;3:667-81 pubmed publisher
    ..Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD. ..
  3. Bouskila M, Hunter R, Ibrahim A, Delattre L, Peggie M, van Diepen J, et al. Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. Cell Metab. 2010;12:456-66 pubmed publisher
    ..Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo. ..
  4. Pederson B, Chen H, Schroeder J, Shou W, DePaoli Roach A, Roach P. Abnormal cardiac development in the absence of heart glycogen. Mol Cell Biol. 2004;24:7179-87 pubmed
    ..Mice lacking this glucose reserve in muscle, heart, and several other tissues were generated by disruption of the GYS1 gene, which encodes an isoform of glycogen synthase...
  5. Duran J, Gruart A, Garcia Rocha M, Delgado Garcia J, Guinovart J. Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease. Hum Mol Genet. 2014;23:3147-56 pubmed publisher
    ..These results identify the regulation of glycogen synthesis as a key target for the treatment of Lafora disease. ..
  6. Tan E, Hooi S, Laban M, Wong E, Ponniah S, Wee A, et al. CCAAT/enhancer binding protein alpha knock-in mice exhibit early liver glycogen storage and reduced susceptibility to hepatocellular carcinoma. Cancer Res. 2005;65:10330-7 pubmed
    ..Our data establish that controlled C/EBPalpha production can inhibit liver tumor growth in vivo. ..
  7. Seldin M, Mott D, Bhat D, Petro A, Kuhn C, Kingsmore S, et al. Glycogen synthase: a putative locus for diet-induced hyperglycemia. J Clin Invest. 1994;94:269-76 pubmed
    ..These data, taken together, raise the possibility that defects in the Gys gene may in part be responsible for the propensity to develop type 2 diabetes. ..
  8. Hunter R, Treebak J, Wojtaszewski J, Sakamoto K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes. 2011;60:766-74 pubmed publisher
    ..We provide genetic evidence that AMPK activation promotes muscle glycogen accumulation by allosteric activation of GS through an increase in glucose uptake and subsequent rise in cellular [G6P]. ..
  9. Kim M, Hunter R, Garcia Menendez L, Gong G, Yang Y, Kolwicz S, et al. Mutation in the ?2-subunit of AMP-activated protein kinase stimulates cardiomyocyte proliferation and hypertrophy independent of glycogen storage. Circ Res. 2014;114:966-75 pubmed publisher
    ..Our study reveals a novel mechanism for Prkag2 cardiomyopathy, independent of glycogen storage. The role of ?2-AMP-activated protein kinase in cell growth also has broad implications in cardiac development, growth, and regeneration. ..

More Information


  1. Antos C, McKinsey T, Frey N, Kutschke W, McAnally J, Shelton J, et al. Activated glycogen synthase-3 beta suppresses cardiac hypertrophy in vivo. Proc Natl Acad Sci U S A. 2002;99:907-12 pubmed
  2. Pederson B, Cope C, Irimia J, Schroeder J, Thurberg B, DePaoli Roach A, et al. Mice with elevated muscle glycogen stores do not have improved exercise performance. Biochem Biophys Res Commun. 2005;331:491-6 pubmed
    ..This result suggests that increased muscle glycogen stores do not necessarily improve exercise performance in mice. ..
  3. Parker G, Pederson B, Obayashi M, Schroeder J, Harris R, Roach P. Gene expression profiling of mice with genetically modified muscle glycogen content. Biochem J. 2006;395:137-45 pubmed
    ..Particularly interesting is the observation that 11 of these genes encode cardiac or slow-twitch isoforms of muscle contractile proteins, and are upregulated in muscle that has a greater oxidative capacity in MGSKO mice. ..
  4. Villarroel Espíndola F, Maldonado R, Mancilla H, Vander Stelt K, Acuña A, Covarrubias A, et al. Muscle glycogen synthase isoform is responsible for testicular glycogen synthesis: glycogen overproduction induces apoptosis in male germ cells. J Cell Biochem. 2013;114:1653-64 pubmed publisher
    ..The rate-limiting enzyme in glycogen synthesis is glycogen synthase (GS). It is encoded by two genes, GYS1, expressed in muscle (muscle glycogen synthase, MGS) and other tissues, and GYS2, primarily expressed in liver (..
  5. Skurat A, Dietrich A, Roach P. Interaction between glycogenin and glycogen synthase. Arch Biochem Biophys. 2006;456:93-7 pubmed
    ..We demonstrate that the COOH-terminal fragment of glycogenin can be used as an effective high affinity reagent for the purification of glycogen synthase from skeletal muscle and liver. ..
  6. Tunster S, Tycko B, John R. The imprinted Phlda2 gene regulates extraembryonic energy stores. Mol Cell Biol. 2010;30:295-306 pubmed publisher
  7. Bajaj N, Miller C. Phosphorylation of neurofilament heavy-chain side-arm fragments by cyclin-dependent kinase-5 and glycogen synthase kinase-3alpha in transfected cells. J Neurochem. 1997;69:737-43 pubmed
    ..Using the transfected fragments, we also map the epitopes for several commonly utilised NF-H monoclonal antibodies and describe the effects that phosphorylation by cdk-5 and GSK-3alpha have on their reactivities. ..
  8. Pederson B, Csitkovits A, Simon R, Schroeder J, Wang W, Skurat A, et al. Overexpression of glycogen synthase in mouse muscle results in less branched glycogen. Biochem Biophys Res Commun. 2003;305:826-30 pubmed
    ..However, this compared with an increase in glycogen synthase of some 50-fold, so that the increase in branching enzyme in response to overexpression of glycogen synthase was insufficient to synthesize normally branched glycogen. ..
  9. Pederson B, Cope C, Schroeder J, Smith M, Irimia J, Thurberg B, et al. Exercise capacity of mice genetically lacking muscle glycogen synthase: in mice, muscle glycogen is not essential for exercise. J Biol Chem. 2005;280:17260-5 pubmed
    ..The MGSKO mouse has the GYS1 gene, encoding the muscle isoform of glycogen synthase, disrupted so that skeletal muscle totally lacks glycogen...
  10. Mora A, Sakamoto K, McManus E, Alessi D. Role of the PDK1-PKB-GSK3 pathway in regulating glycogen synthase and glucose uptake in the heart. FEBS Lett. 2005;579:3632-8 pubmed
  11. Sinadinos C, Valles Ortega J, Boulan L, Solsona E, Tevy M, Marquez M, et al. Neuronal glycogen synthesis contributes to physiological aging. Aging Cell. 2014;13:935-45 pubmed publisher
    ..These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. ..
  12. Turnbull J, Tiberia E, Pereira S, Zhao X, Pencea N, Wheeler A, et al. Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance. J Biol Chem. 2013;288:34627-37 pubmed publisher
    ..Our work identifies a novel GS-associated GS activity-modulating component of insulin resistance. ..
  13. Akman H, Sheiko T, Tay S, Finegold M, DiMauro S, Craigen W. Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV. Hum Mol Genet. 2011;20:4430-9 pubmed publisher
    ..Both mouse models recapitulate typical histological and physiological features of two human variants of branching enzyme deficiency. ..
  14. Nakano K, Takeshita S, Kawasaki N, Miyanaga W, Okamatsu Y, Dohi M, et al. AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice. Int J Mol Med. 2017;39:841-850 pubmed publisher
    ..In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated ..
  15. Douillard Guilloux G, Raben N, Takikita S, Ferry A, Vignaud A, Guillet Deniau I, et al. Restoration of muscle functionality by genetic suppression of glycogen synthesis in a murine model of Pompe disease. Hum Mol Genet. 2010;19:684-96 pubmed publisher
    ..GAA and glycogen synthase 1 (GYS1) KO mice were inter-crossed to generate a new double-KO model...
  16. Cheng A, Zhang M, Gentry M, Worby C, Dixon J, Saltiel A. A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease. Genes Dev. 2007;21:2399-409 pubmed
    ..Taken together, these results indicate that binding to glycogen crucially regulates the stability of AGL and, further, that its ubiquitination may play an important role in the pathophysiology of both Lafora and Cori's disease. ..
  17. Pescador N, Villar D, Cifuentes D, Garcia Rocha M, Ortiz Barahona A, Vazquez S, et al. Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1. PLoS ONE. 2010;5:e9644 pubmed publisher
    ..Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter...
  18. Duran J, Saez I, Gruart A, Guinovart J, Delgado Garcia J. Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J Cereb Blood Flow Metab. 2013;33:550-6 pubmed publisher
    ..To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1(Nestin-KO)) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving ..
  19. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol. 1998;14:59-88 pubmed
    ..Here we review recent data that have started to unravel the mechanisms of Wnt signaling. ..
  20. Cifuentes D, Martínez Pons C, Garcia Rocha M, Galina A, Ribas De Pouplana L, Guinovart J. Hepatic glycogen synthesis in the absence of glucokinase: the case of embryonic liver. J Biol Chem. 2008;283:5642-9 pubmed publisher
    ..Moreover, the physiological consequence of the HK isoform switch is that the embryonic liver safeguards its glycogen deposits, required as the main source of energy at birth, from maternal starvation. ..
  21. Wang W, Parker G, Skurat A, Raben N, DePaoli Roach A, Roach P. Relationship between glycogen accumulation and the laforin dual specificity phosphatase. Biochem Biophys Res Commun. 2006;350:588-92 pubmed
    ..We propose, therefore, that laforin senses cytosolic glycogen accumulation which in turn determines the level of laforin protein. ..
  22. Pederson B, Schroeder J, Parker G, Smith M, DePaoli Roach A, Roach P. Glucose metabolism in mice lacking muscle glycogen synthase. Diabetes. 2005;54:3466-73 pubmed
    ..MGSKO mice lack skeletal muscle glycogen due to disruption of the GYS1 gene, which encodes muscle glycogen synthase...
  23. Azpiazu I, Manchester J, Skurat A, Roach P, Lawrence J. Control of glycogen synthesis is shared between glucose transport and glycogen synthase in skeletal muscle fibers. Am J Physiol Endocrinol Metab. 2000;278:E234-43 pubmed
  24. Pellegri G, Rossier C, Magistretti P, Martin J. Cloning, localization and induction of mouse brain glycogen synthase. Brain Res Mol Brain Res. 1996;38:191-9 pubmed
    ..Vasoactive intestinal peptide and noradrenaline, two neurotransmitters previously shown to induce a glycogen resynthesis in cultured astrocytes, upregulate the expression of glycogen synthase mRNA in this cell type but not in neurons. ..
  25. Kuma Y, Campbell D, Cuenda A. Identification of glycogen synthase as a new substrate for stress-activated protein kinase 2b/p38beta. Biochem J. 2004;379:133-9 pubmed
    ..These results suggest that SAPK2b/p38b may be a priming kinase that allows glycogen synthase kinase 3 to phosphorylate Ser640 and thereby inhibit glycogen synthase activity. ..
  26. Mir Coll J, Duran J, Slebe F, García Rocha M, Gomis R, Gasa R, et al. Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis. Diabetologia. 2016;59:1012-20 pubmed publisher
    ..Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using ..