HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive exercise of wild type and laforin knockout mice.

Abstract
Glycogen, the repository of glucose in many cell types, contains small amounts of covalent phosphate, of uncertain function and poorly understood metabolism. Loss-of-function mutations in the laforin gene cause the fatal neurodegenerative disorder, Lafora disease, characterized by increased glycogen phosphorylation and the formation of abnormal deposits of glycogen-like material called Lafora bodies. It is generally accepted that the phosphate is removed by the laforin phosphatase. To study the dynamics of skeletal muscle glycogen phosphorylation in vivo under physiological conditions, mice were subjected to glycogen-depleting exercise and then monitored while they resynthesized glycogen. Depletion of glycogen by exercise was associated with a substantial reduction in total glycogen phosphate and the newly resynthesized glycogen was less branched and less phosphorylated. Branching returned to normal on a time frame of days, whereas phosphorylation remained suppressed over a longer period of time. We observed no change in markers of autophagy. Exercise of 3-month-old laforin knock-out mice caused a similar depletion of glycogen but no loss of glycogen phosphate. Furthermore, remodeling of glycogen to restore the basal branching pattern was delayed in the knock-out animals. From these results, we infer that 1) laforin is responsible for glycogen dephosphorylation during exercise and acts during the cytosolic degradation of glycogen, 2) excess glycogen phosphorylation in the absence of laforin delays the normal remodeling of the branching structure, and 3) the accumulation of glycogen phosphate is a relatively slow process involving multiple cycles of glycogen synthesis-degradation, consistent with the slow onset of the symptoms of Lafora disease.
AuthorsJose M Irimia, Vincent S Tagliabracci, Catalina M Meyer, Dyann M Segvich, Anna A DePaoli-Roach, Peter J Roach
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 37 Pg. 22686-98 (Sep 11 2015) ISSN: 1083-351X [Electronic] United States
PMID26216881 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Chemical References
  • Glycogen
  • Dual-Specificity Phosphatases
  • Epm2a protein, mouse
  • Protein Tyrosine Phosphatases, Non-Receptor
Topics
  • Animals
  • Dual-Specificity Phosphatases (genetics, metabolism)
  • Glycogen (genetics, metabolism)
  • Lafora Disease (genetics, metabolism, pathology)
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal (metabolism, pathology)
  • Phosphorylation (genetics)
  • Physical Conditioning, Animal
  • Protein Tyrosine Phosphatases, Non-Receptor

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: