{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:45:28Z","timestamp":1791153928757,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"49","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,12,4]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>EPM2A<\/jats:italic>\n                    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\n                    <jats:italic>in vitro<\/jats:italic>\n                    , in a time-dependent reaction with an apparent\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0707952104","type":"journal-article","created":{"date-parts":[[2007,11,27]],"date-time":"2007-11-27T00:09:15Z","timestamp":1196122155000},"page":"19262-19266","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":184,"title":["Laforin is a glycogen phosphatase, deficiency of which leads to elevated phosphorylation of glycogen\n                    <i>in vivo<\/i>"],"prefix":"10.1073","volume":"104","author":[{"given":"Vincent S.","family":"Tagliabracci","sequence":"first","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Turnbull","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Girard","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochu","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Skurat","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio 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