Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy

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dc.contributor.authorVilchez, David
dc.contributor.authorRos, Susana
dc.contributor.authorCifuentes, Daniel
dc.contributor.authorPujadas, Lluís
dc.contributor.authorVallès, Jordi
dc.contributor.authorGarcía-Fojeda García-Valdecasas, María Belén
dc.contributor.authorCriado-García, Olga
dc.contributor.authorFernández-Sánchez, Elena
dc.contributor.authorMedraño-Fernández, Iria
dc.contributor.authorDomínguez, Jorge
dc.contributor.authorGarcía-Rocha, Mar
dc.contributor.authorSoriano, Eduardo
dc.contributor.authorRodríguez de Córdoba, Santiago
dc.contributor.authorGuinovart, Joan
dc.date.accessioned2024-02-02T12:18:40Z
dc.date.available2024-02-02T12:18:40Z
dc.date.issued2007
dc.description.abstractGlycogen synthesis is normally absent in neurons. However, inclusion bodies resembling abnormal glycogen accumulate in several neurological diseases, particularly in progressive myoclonus epilepsy or Lafora disease. We show here that mouse neurons have the enzymatic machinery for synthesizing glycogen, but that it is suppressed by retention of muscle glycogen synthase (MGS) in the phosphorylated, inactive state. This suppression was further ensured by a complex of laforin and malin, which are the two proteins whose mutations cause Lafora disease. The laforin-malin complex caused proteasome-dependent degradation both of the adaptor protein targeting to glycogen, PTG, which brings protein phosphatase 1 to MGS for activation, and of MGS itself. Enforced expression of PTG led to glycogen deposition in neurons and caused apoptosis. Therefore, the malin-laforin complex ensures a blockade of neuronal glycogen synthesis even under intense glycogenic conditions. Here we explain the formation of polyglucosan inclusions in Lafora disease by demonstrating a crucial role for laforin and malin in glycogen synthesis.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Educación y Ciencia (España)
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipFundació La Caixa
dc.description.sponsorshipFundació La Marató de TV3
dc.description.sponsorshipFundación Marcelino Botín
dc.description.statuspub
dc.identifier.citationVilchez, D., Ros, S., Cifuentes, D. et al. Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat Neurosci 10, 1407–1413 (2007). https://doi.org/10.1038/nn1998
dc.identifier.doi10.1038/nn1998
dc.identifier.essn1546-1726
dc.identifier.issn1097-6256
dc.identifier.officialurlhttps://doi.org/10.1038/nn1998
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/17952067/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/98244
dc.issue.number11
dc.journal.titleNature Neuroscience
dc.language.isoeng
dc.page.final1413
dc.page.initial1407
dc.publisherSpringer Nature
dc.relation.projectIDSAF2005-00913
dc.relation.projectIDBFU2005-02253
dc.relation.projectIDCIBER-ER: RD06/0015/0030
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsmetadata only access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu577.1
dc.subject.cdu577.2
dc.subject.cdu575
dc.subject.cdu612.8
dc.subject.keywordGlycogen
dc.subject.keywordNeurons
dc.subject.keywordLafora disease
dc.subject.keywordGlycogen synthase
dc.subject.keywordLaforin
dc.subject.keywordMalin
dc.subject.keywordProtein targeting to glycogen
dc.subject.keywordProtein phosphatase 1
dc.subject.keywordProteasome-dependent degradation
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmBiología molecular (Biología)
dc.subject.ucmNeurociencias (Biológicas)
dc.subject.ucmGenética
dc.subject.unesco2403 Bioquímica
dc.subject.unesco2415 Biología Molecular
dc.subject.unesco2409 Genética
dc.subject.unesco2407.01 Cultivo Celular
dc.titleMechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number10
dspace.entity.typePublication
relation.isAuthorOfPublication89ed03ac-f011-4290-9a31-7390e12f1724
relation.isAuthorOfPublication.latestForDiscovery89ed03ac-f011-4290-9a31-7390e12f1724
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