Muscle glycogenoses

DiMauro, Salvatore; Lamperti, Costanza

doi:10.1002/mus.1103

Cited by 120 publications

(81 citation statements)

References 147 publications

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“…With regard to the latter proposition, it is interesting that Stbd1 binds better to plant amylopectin or glycogen from Epm2a Ϫ/Ϫ mice. Both amylopectin and Epm2a Ϫ/Ϫ glycogen are less branched than normal glycogen, similar to the polyglucosans associated with other glycogen storage diseases, including Andersen disease, Adult polyglucosan disease, and Tarui disease (51). Evidently, aberrantly branched glycogen in cells is to be avoided, and Stbd1 could selectively target such abnormal glycogen for transport to lysosomes and for subsequent disposal.…”

Section: Discussionmentioning

confidence: 92%

Starch Binding Domain-containing Protein 1/Genethonin 1 Is a Novel Participant in Glycogen Metabolism

Jiang

Heller

Tagliabracci

et al. 2010

Journal of Biological Chemistry

127

118

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Stbd1 is a protein of previously unknown function that is most prevalent in liver and muscle, the major sites for storage of the energy reserve glycogen. The protein is predicted to contain a hydrophobic N terminus and a C-terminal CBM20 glycan binding domain. Here, we show that Stbd1 binds to glycogen in vitro and that endogenous Stbd1 locates to perinuclear compartments in cultured mouse FL83B or Rat1 cells. When overexpressed in COSM9 cells, Stbd1 concentrated at enlarged perinuclear structures, co-localized with glycogen, the late endosomal/lysosomal marker LAMP1 and the autophagy protein GABARAPL1. Mutant Stbd1 lacking the N-terminal hydrophobic segment had a diffuse distribution throughout the cell. Point mutations in the CBM20 domain did not change the perinuclear localization of Stbd1, but glycogen was no longer concentrated in this compartment. Stable overexpression of glycogen synthase in Rat1WT4 cells resulted in accumulation of glycogen as massive perinuclear deposits, where a large fraction of the detectable Stbd1 co-localized. Starvation of Rat1WT4 cells for glucose resulted in dissipation of the massive glycogen stores into numerous and much smaller glycogen deposits that retained Stbd1. In vitro, in cells, and in animal models, Stbd1 consistently tracked with glycogen. We conclude that Stbd1 is involved in glycogen metabolism by binding to glycogen and anchoring it to membranes, thereby affecting its cellular localization and its intracellular trafficking to lysosomes.

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Section: Discussionmentioning

confidence: 92%

Starch Binding Domain-containing Protein 1/Genethonin 1 Is a Novel Participant in Glycogen Metabolism

Jiang

Heller

Tagliabracci

et al. 2010

Journal of Biological Chemistry

127

118

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“…Interestingly a general impairment of energy metabolism have been observed in conditions of muscle atrophy [29], which may develop also during statin myopathy [50]. Moreover, it has been shown that hereditary muscle glycogenoses in humans are characterized by defective glycolytic enzymes, including beta enolase, and leads to different degree of myopathy, ranging from cramps to myoglobinuria [51][52]. The PK is a key enzyme in the glycolytic pathway, being responsible for the synthesis of pyruvate and ATP formation; it is allosterically inhibited by the increase in acetyl CoA, which in this condition may be induced by the block of cholesterol pathway in the cytosol.…”

Section: Glycolytic Metabolismmentioning

confidence: 99%

Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle

Camerino

Pellegrino

Brocca

et al. 2011

Biochemical Pharmacology

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Statins and fibrates can cause myopathy. To further understand the causes of the damage we performed a proteome analysis in fast-twitch skeletal muscle of rats chronically treated with different hypolipidemic drugs. The proteomic maps were obtained from extensor digitorum longus (EDL) muscles of rats treated for 2-months with 10mg/kg atorvastatin, 20mg/kg fluvastatin, 60mg/kg fenofibrate and control rats. The proteins differentially expressed were identified by mass spectrometry and further analysed by immunoblot analysis. We found a significant modification in 40 out of 417 total spots analysed in atorvastatin treated rats, 15 out of 436 total spots in fluvastatin treated rats and 21 out of 439 total spots in fenofibrate treated rats in comparison to controls. All treatments induced a general tendency to a down-regulation of protein expression; in particular, atorvastatin affected the protein pattern more extensively with respect to the other treatments.Energy production systems, both oxidative and glycolytic enzymes and creatine kinase, were downregulated following atorvastatin administration, whereas fenofibrate determined mostly alterations in glycolytic enzymes and creatine kinase, oxidative enzymes being relatively spared. Additionally, all treatments resulted in some modifications of proteins involved in cellular defenses against oxidative stress, such as heat shock proteins, and of myofibrillar proteins. These results were confirmed by immunoblot analysis. In conclusions, the proteomic analysis showed that either statin or fibrate administration can modify the expression of proteins essential for skeletal muscle function suggesting potential mechanisms for statin myopathy.

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“…The primary polymerization in glycogen is via ␣-1,4-glycosidic linkages, formed by the action of glycogen synthase, with branchpoints created by ␣-1,6-glycosidic linkages introduced by the branching enzyme (1). Mutations in these and other glycogen metabolizing enzymes result in a series of glycogen storage diseases characterized by aberrant glycogen deposits (2)(3)(4). Lafora disease (OMIM254780) is an autosomal recessive juvenile-onset myoclonus epilepsy that, although not normally viewed as a classic example of a glycogenosis, nonetheless is characterized by abnormal glycogen accumulation.…”

mentioning

confidence: 99%

Laforin is a glycogen phosphatase, deficiency of which leads to elevated phosphorylation of glycogen in vivo

Tagliabracci

Turnbull

Wang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

189

237

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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 Km 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.polyglucosan ͉ Lafora bodies ͉ Epm2a ͉ phosphate

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Muscle glycogenoses

Cited by 120 publications

References 147 publications

Starch Binding Domain-containing Protein 1/Genethonin 1 Is a Novel Participant in Glycogen Metabolism

Starch Binding Domain-containing Protein 1/Genethonin 1 Is a Novel Participant in Glycogen Metabolism

Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle

Laforin is a glycogen phosphatase, deficiency of which leads to elevated phosphorylation of glycogen in vivo

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