Relationship between glycogen accumulation and the laforin dual specificity phosphatase

Wei Wang, Gretchen E. Parker, Alexander V. Skurat, Nina Raben, Anna A. DePaoli-Roach, Peter J. Roach

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Laforin, encoded by the EPM2A gene, is a dual specificity protein phosphatase that has a functional glycogen-binding domain. Mutations in the EPM2A gene account for around half of the cases of Lafora disease, an autosomal recessive neurodegenerative disorder, characterized by progressive myoclonus epilepsy. The hallmark of the disease is the presence of Lafora bodies, which contain polyglucosan, a poorly branched form of glycogen, in neurons and other tissues. We examined the level of laforin protein in several mouse models in which muscle glycogen accumulation has been altered genetically. Mice with elevated muscle glycogen have increased laforin as judged by Western analysis. Mice completely lacking muscle glycogen or with 10% normal muscle glycogen had reduced laforin. Mice defective in the GAA gene encoding lysosomal α-glucosidase (acid maltase) overaccumulate glycogen in the lysosome but did not have elevated laforin. We propose, therefore, that laforin senses cytosolic glycogen accumulation which in turn determines the level of laforin protein.

Original languageEnglish (US)
Pages (from-to)588-592
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume350
Issue number3
DOIs
StatePublished - Nov 24 2006

Fingerprint

Dual-Specificity Phosphatases
Glycogen
Muscle
Muscles
Lafora Disease
Genes
Progressive Myoclonic Epilepsy
Glucosidases
Gene encoding
alpha-Glucosidases
Phosphoprotein Phosphatases
Lysosomes
Neurodegenerative Diseases
Neurons
Proteins
Tissue
Mutation

Keywords

  • Glycogen
  • Lafora disease
  • Laforin
  • Protein phosphatase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Relationship between glycogen accumulation and the laforin dual specificity phosphatase. / Wang, Wei; Parker, Gretchen E.; Skurat, Alexander V.; Raben, Nina; DePaoli-Roach, Anna A.; Roach, Peter J.

In: Biochemical and Biophysical Research Communications, Vol. 350, No. 3, 24.11.2006, p. 588-592.

Research output: Contribution to journalArticle

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