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Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
Skeletal Muscle Glycogen Chain Length Correlates with Insolubility in Mouse Models of Polyglucosan-Associated Neurodegenerative Diseases
Cell Reports , Vol.27(5), pp.1334-1344.e6
2019
PMID: 31042462
Abstract
Lafora disease (LD) and adult polyglucosan body disease (APBD) are glycogen storage diseases characterized by a pathogenic buildup of insoluble glycogen. Mechanisms causing glycogen insolubility are poorly understood. Here, in two mouse models of LD (Epm2a−/− and Epm2b−/−) and one of APBD (Gbe1ys/ys), the separation of soluble and insoluble muscle glycogen is described, enabling separate analysis of each fraction. Total glycogen is increased in LD and APBD mice, which, together with abnormal chain length and molecule size distributions, is largely if not fully attributed to insoluble glycogen. Soluble glycogen consists of molecules with distinct chain length distributions and differential corresponding solubility, providing a mechanistic link between soluble and insoluble glycogen in vivo. Phosphorylation states differ across glycogen fractions and mouse models, demonstrating that hyperphosphorylation is not a basic feature of insoluble glycogen. Lastly, model-specific variances in protein and activity levels of key glycogen synthesis enzymes suggest uninvestigated regulatory mechanisms.
Details
- Title
- Skeletal Muscle Glycogen Chain Length Correlates with Insolubility in Mouse Models of Polyglucosan-Associated Neurodegenerative Diseases
- Authors
- Mitchell A Sullivan - Hospital for Sick ChildrenSilvia Nitschke - Hospital for Sick ChildrenEvan P. Skwara - Hospital for Sick ChildrenPeixiang Wang - Hospital for Sick ChildrenXiaochu Zhao - Hospital for Sick ChildrenXiao S. Pan - Hospital for Sick ChildrenErin E Chown - Hospital for Sick ChildrenTravis Wang - Hospital for Sick ChildrenAmi M Perri - Hospital for Sick ChildrenJennifer P.Y. Lee - Hospital for Sick ChildrenFrancisco Vilaplana - KTH Royal Institute of TechnologyBerge A Minassian - Hospital for Sick ChildrenFelix Nitschke (Corresponding Author) - Hospital for Sick Children
- Publication details
- Cell Reports , Vol.27(5), pp.1334-1344.e6
- Publisher
- Cell Press
- Date published
- 2019
- DOI
- 10.1016/j.celrep.2019.04.017
- ISSN
- 2211-1247
- PMID
- 31042462
- Copyright note
- (c) 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991035096102621
- Output Type
- Journal article
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