| http://purl.uniprot.org/citations/18040046 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18040046 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18040046 | http://www.w3.org/2000/01/rdf-schema#comment | "Lafora disease is a progressive myoclonus epilepsy with onset typically in the second decade of life and death within 10 years. Lafora bodies, deposits of abnormally branched, insoluble glycogen-like polymers, form in neurons, muscle, liver, and other tissues. Approximately half of the cases of Lafora disease result from mutations in the EPM2A gene, which encodes laforin, a member of the dual-specificity protein phosphatase family that additionally contains a glycogen binding domain. The molecular basis for the formation of Lafora bodies is completely unknown. Glycogen, a branched polymer of glucose, contains a small amount of covalently linked phosphate whose origin and function are obscure. We report here that recombinant laforin is able to release this phosphate in vitro, in a time-dependent reaction with an apparent K(m) for glycogen of 4.5 mg/ml. Mutations of laforin that disable the glycogen binding domain also eliminate its ability to dephosphorylate glycogen. We have also analyzed glycogen from a mouse model of Lafora disease, Epm2a(-/-) mice, which develop Lafora bodies in several tissues. Glycogen isolated from these mice had a 40% increase in the covalent phosphate content in liver and a 4-fold elevation in muscle. We propose that excessive phosphorylation of glycogen leads to aberrant branching and Lafora body formation. This study provides a molecular link between an observed biochemical property of laforin and the phenotype of a mouse model of Lafora disease. The results also have important implications for glycogen metabolism generally."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0707952104"xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0707952104"xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Depaoli-Roach A.A."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Depaoli-Roach A.A."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Wang W."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Wang W."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Zhao X."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Zhao X."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Minassian B.A."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Minassian B.A."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Tagliabracci V.S."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Tagliabracci V.S."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Turnbull J."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Turnbull J."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Roach P.J."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Roach P.J."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Delgado-Escueta A.V."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Delgado-Escueta A.V."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Skurat A.V."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Skurat A.V."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Girard J.M."xsd:string |
| http://purl.uniprot.org/citations/18040046 | http://purl.uniprot.org/core/author | "Girard J.M."xsd:string |