TY - JOUR
T1 - Glycogen metabolism in tissues from a mouse model of Lafora disease
AU - Wang, Wei
AU - Lohi, Hannes
AU - Skurat, Alexander V.
AU - DePaoli-Roach, Anna A.
AU - Minassian, Berge A.
AU - Roach, Peter J.
N1 - Funding Information:
Supported by NIH Grants DK27221 (P.J.R.), DK36569 (A.D.R.), an American Heart Association Fellowship (W.W.), the Canadian Institutes of Health Research (B.A.M), and the Sigrid Juselius and Emil Aaltonen Foundations (H.L.)
PY - 2007/1/15
Y1 - 2007/1/15
N2 - Laforin, encoded by the EPM2A gene, by sequence is a member of the dual specificity protein phosphatase family. 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, muscle and other tissues. Glycogen metabolizing enzymes were analyzed in a transgenic mouse over-expressing a dominant negative form of laforin that accumulates Lafora bodies in several tissues. Skeletal muscle glycogen was increased 2-fold as was the total glycogen synthase protein. However, the -/+glucose-6-P activity of glycogen synthase was decreased from 0.29 to 0.16. Branching enzyme activity was increased by 30%. Glycogen phosphorylase activity was unchanged. In whole brain, no differences in glycogen synthase or branching enzyme activities were found. Although there were significant differences in enzyme activities in muscle, the results do not support the hypothesis that Lafora body formation is caused by a major change in the balance between glycogen elongation and branching activities.
AB - Laforin, encoded by the EPM2A gene, by sequence is a member of the dual specificity protein phosphatase family. 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, muscle and other tissues. Glycogen metabolizing enzymes were analyzed in a transgenic mouse over-expressing a dominant negative form of laforin that accumulates Lafora bodies in several tissues. Skeletal muscle glycogen was increased 2-fold as was the total glycogen synthase protein. However, the -/+glucose-6-P activity of glycogen synthase was decreased from 0.29 to 0.16. Branching enzyme activity was increased by 30%. Glycogen phosphorylase activity was unchanged. In whole brain, no differences in glycogen synthase or branching enzyme activities were found. Although there were significant differences in enzyme activities in muscle, the results do not support the hypothesis that Lafora body formation is caused by a major change in the balance between glycogen elongation and branching activities.
KW - Branching enzyme
KW - Dual specificity phosphatase
KW - Glycogen
KW - Glycogen synthase
KW - Glycogen synthase kinase-3
KW - Lafora disease
KW - Laforin
UR - http://www.scopus.com/inward/record.url?scp=33845986675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845986675&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2006.10.017
DO - 10.1016/j.abb.2006.10.017
M3 - Article
C2 - 17118331
AN - SCOPUS:33845986675
SN - 0003-9861
VL - 457
SP - 264
EP - 269
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -