Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Laforin

  • M. Kathryn Brewer
  • Amanda R. Sherwood
  • Vikas V. Dukhande
  • Matthew S. Gentry
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_603

Synonyms

Historical Background

Two groups searching for genes mutated in Lafora disease patients independently discovered the EPM2A ( epilepsy, progressive myoclonic type 2A) gene, and the protein it encoded was aptly named laforin (Serratosa et al. 1995; Minassian et al. 1998). Laforin is a bimodular protein containing a dual specificity phosphatase (DSP) domain and a carbohydrate-binding module (CBM) (Fig. 1) (Minassian et al. 1998, Wang et al. 2002). Dual specificity phosphatases (DSPs) are a diverse group of phosphatases whose members dephosphorylate phosphoserine/phosphothreonine (pSer/pThr), phosphotyrosine (pTyr), phosphoinositols, ribo/deoxyribonucleotide 5′-triphosphates, pyrophosphate/triphosphate, or phosphoglucans. DSPs are members of the larger protein tyrosine phosphatase (PTP) superfamily that all utilize a cysteine-dependent mechanism to hydrolyze phosphoester bonds (Tonks 2006). This mechanism is dependent on the conserved CX 5R active site...
This is a preview of subscription content, log in to check access.

References

  1. Aguado C, Sarkar S, Korolchuk VI, Criado O, Vernia S, Boya P, et al. Laforin, the most common protein mutated in Lafora disease, regulates autophagy. Hum Mol Genet. 2010;19(14):2867–76.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Berkovic SF, Andermann F, Carpenter S, Wolfe LS. Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med. 1986;315(5):296–305.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Berkovic SF, So NK, Andermann F. Progressive myoclonus epilepsies: clinical and neurophysiological diagnosis. J Clin Neurophysiol. 1991;8(3):261–74.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bertoft E. Fine structure of amylopectin. In: Starch: metabolism and structure. Tokyo: Springer; 2015. p. 3–40.CrossRefGoogle Scholar
  5. Blennow A. Phosphorylation of the starch granule. In: Starch. Springer: Tokyo; 2015. p. 399–424.CrossRefGoogle Scholar
  6. Blennow A, Engelsen SB. Helix-breaking news: fighting crystalline starch energy deposits in the cell. Trends Plant Sci. 2010;15(4):236–40.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Brewer MK, Husodo S, Dukhande VV, Johnson MB, Gentry MS. Expression, purification and characterization of soluble red rooster laforin as a fusion protein in Escherichia coli. BMC Biochem. 2014;15:8.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Brown AM. Brain glycogen re-awakened. J Neurochem. 2004;89(3):537–52.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bultot L, Guigas B, Von Wilamowitz-Moellendorff A, Maisin L, Vertommen D, Hussain N, et al. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase. Biochem J. 2012;443(1):193–203.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B. The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 2009;37(Database issue):D233–8.CrossRefPubMedGoogle Scholar
  11. Chan EM, Young EJ, Ianzano L, Munteanu I, Zhao X, Christopoulos CC, et al. Mutations in NHLRC1 cause progressive myoclonus epilepsy. Nat Genet. 2003;35(2):125–7.CrossRefPubMedGoogle Scholar
  12. Chan EM, Ackerley CA, Lohi H, Ianzano L, Cortez MA, Shannon P, et al. Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy. Hum Mol Genet. 2004;13(11):1117–29.CrossRefPubMedGoogle Scholar
  13. Chen ZJ, Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell. 2009;33(3):275–86.CrossRefPubMedGoogle Scholar
  14. Cheng A, Zhang M, Gentry MS, Worby CA, Dixon JE, Saltiel AR. A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori’s disease. Genes Dev. 2007;21(19):2399–409.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Contreras CJ, Segvich DM, Mahalingan K, Chikwana VM, Kirley TL, Hurley TD, et al. Incorporation of phosphate into glycogen by glycogen synthase. Arch Biochem Biophys. 2016;597:21–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Criado O, Aguado C, Gayarre J, Duran-Trio L, Garcia-Cabrero AM, Vernia S, et al. Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy. Hum Mol Genet. 2012;21(7):1521–33.CrossRefPubMedGoogle Scholar
  17. DePaoli-Roach AA, Tagliabracci VS, Segvich DM, Meyer CM, Irimia JM, Roach PJ. Genetic depletion of the malin E3 ubiquitin ligase in mice leads to lafora bodies and the accumulation of insoluble laforin. J Biol Chem. 2010;285(33):25372–81.PubMedPubMedCentralCrossRefGoogle Scholar
  18. DePaoli-Roach AA, Contreras CJ, Segvich DM, Heiss C, Ishihara M, Azadi P, et al. Glycogen phosphomonoester distribution in mouse models of the progressive myoclonic epilepsy, Lafora disease. J Biol Chem. 2014;290(2):841–50.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Dias DM, Furtado J, Wasielewski E, Cruz R, Costello B, Cole L, et al. Biophysical characterization of laforin-carbohydrate interaction. Biochem J. 2015;473(3):335–45.CrossRefPubMedGoogle Scholar
  20. Dinuzzo M, Mangia S, Maraviglia B, Giove F. Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy? Metab Brain Dis. 2014a;30(1):307–16.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Dinuzzo M, Mangia S, Maraviglia B, Giove F. Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy. Epilepsy Res. 2014b;108(6):995–1012.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dubey D, Ganesh S. Modulation of functional properties of laforin phosphatase by alternative splicing reveals a novel mechanism for the EPM2A gene in Lafora progressive myoclonus epilepsy. Hum Mol Genet. 2008;17(19):3010–20.CrossRefPubMedGoogle Scholar
  23. Dubey D, Parihar R, Ganesh S. Identification and characterization of novel splice variants of the human EPM2A gene mutated in Lafora progressive myoclonus epilepsy. Genomics. 2012;99(1):36–43.CrossRefPubMedGoogle Scholar
  24. Dukhande VV, Sherwood AR, Gentry MS. Laforin- nature molecule page. In: Nature molecule pages. 2010. San Diego: Nature Signaling Gateway. doi:10.1038/mp.a000032.01.Google Scholar
  25. Dukhande VV, Rogers DM, Roma-Mateo C, Donderis J, Marina A, Taylor AO, et al. Laforin, a dual specificity phosphatase involved in Lafora disease, is present mainly as monomeric form with full phosphatase activity. PLoS One. 2011;6(8):e24040.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Duran J, Tevy MF, Garcia-Rocha M, Calbo J, Milan M, Guinovart JJ. Deleterious effects of neuronal accumulation of glycogen in flies and mice. EMBO Mol Med. 2012;4(8):719–29.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Duran J, Saez I, Gruart A, Guinovart JJ, Delgado-Garcia JM. Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J Cereb Blood Flow Metab. 2013;33(4):550–6.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Duran J, Gruart A, Garcia-Rocha M, Delgado-Garcia JM, Guinovart JJ. Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease. Hum Mol Genet. 2014;23(12):3147–56.CrossRefPubMedGoogle Scholar
  29. Emanuelle S, Brewer MK, Meekins DA, Gentry MS. Unique carbohydrate binding platforms employed by the glucan phosphatases. Cell Mol Life Sci. 2016;73(14):2765–78.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Fernandez-Sanchez ME, Criado-Garcia O, Heath KE, Garcia-Fojeda B, Medrano-Fernandez I, Gomez-Garre P, et al. Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation. Hum Mol Genet. 2003;12(23):3161–71.CrossRefPubMedGoogle Scholar
  31. Ganesh S, Agarwala KL, Ueda K, Akagi T, Shoda K, Usui T, et al. Laforin, defective in the progressive myoclonus epilepsy of Lafora type, is a dual-specificity phosphatase associated with polyribosomes. Hum Mol Genet. 2000;9(15):2251–61.CrossRefPubMedGoogle Scholar
  32. Ganesh S, Agarwala KL, Amano K, Suzuki T, Delgado-Escueta AV, Yamakawa K. Regional and developmental expression of Epm2a gene and its evolutionary conservation. Biochem Biophys Res Commun. 2001;283(5):1046–53.CrossRefPubMedGoogle Scholar
  33. Ganesh S, Suzuki T, Yamakawa K. Alternative splicing modulates subcellular localization of laforin. Biochem Biophys Res Commun. 2002;291(5):1134–7.CrossRefPubMedGoogle Scholar
  34. Ganesh S, Tsurutani N, Suzuki T, Hoshii Y, Ishihara T, Delgado-Escueta AV, et al. The carbohydrate-binding domain of Lafora disease protein targets Lafora polyglucosan bodies. Biochem Biophys Res Commun. 2004;313(4):1101–9.CrossRefPubMedGoogle Scholar
  35. Ganesh S, Puri R, Singh S, Mittal S, Dubey D. Recent advances in the molecular basis of Lafora’s progressive myoclonus epilepsy. J Hum Genet. 2006;51(1):1–8.CrossRefPubMedGoogle Scholar
  36. Garyali P, Segvich DM, DePaoli-Roach AA, Roach PJ. Protein degradation and quality control in cells from laforin and malin knockout mice. J Biol Chem. 2014;289(30):20606–14.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Gayarre J, Duran-Trio L, Criado Garcia O, Aguado C, Juana-Lopez L, Crespo I, et al. The phosphatase activity of laforin is dispensable to rescue Epm2a−/− mice from Lafora disease. Brain. 2014;137(Pt 3):806–18.CrossRefPubMedGoogle Scholar
  38. Gentry MS, Pace RM. Conservation of the glucan phosphatase laforin is linked to rates of molecular evolution and the glycogen metabolism of the organism. BMC Evol Biol. 2009;9(1):138.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Gentry MS, Worby CA, Dixon JE. Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin. Proc Natl Acad Sci USA. 2005;102(24):8501–6.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Gentry MS, Dowen 3rd RH, Worby CA, Mattoo S, Ecker JR, Dixon JE. The phosphatase laforin crosses evolutionary boundaries and links carbohydrate metabolism to neuronal disease. J Cell Biol. 2007;178(3):477–88.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Gentry MS, Dixon JE, Worby CA. Lafora disease: insights into neurodegeneration from plant metabolism. Trends Biochem Sci. 2009;34(12):628–39.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Gentry MS, Roma-Mateo C, Sanz P. Laforin, a protein with many faces: glucan phosphatase, adapter protein, et alii. FEBS J. 2013;280(2):525–37.CrossRefPubMedGoogle Scholar
  43. Gentry MS, Brewer MK, Vander Kooi CW. Structural biology of glucan phosphatases from humans to plants. Curr Opin Struct Biol. 2016;40:62–9.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Gibbs ME, Lloyd HG, Santa T, Hertz L. Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J Neurosci Res. 2007;85(15):3326–33.CrossRefPubMedGoogle Scholar
  45. Girard JM, Turnbull J, Ramachandran N, Minassian BA. Progressive myoclonus epilepsy. Handb Clin Neurol. 2013;113:1731–6.PubMedCrossRefGoogle Scholar
  46. Graham TE, Yuan Z, Hill AK, Wilson RJ. The regulation of muscle glycogen: the granule and its proteins. Acta Physiol (Oxford). 2010;199(4):489–98.CrossRefGoogle Scholar
  47. Hejazi M, Fettke J, Kotting O, Zeeman SC, Steup M. The Laforin-like dual-specificity phosphatase SEX4 from Arabidopsis hydrolyzes both C6- and C3-phosphate esters introduced by starch-related dikinases and thereby affects phase transition of alpha-glucans. Plant Physiol. 2010;152(2):711–22.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Irimia JM, Tagliabracci VS, Meyer CM, Segvich DM, DePaoli-Roach AA, Roach PJ. Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive exercise of wild type and laforin knockout mice. J Biol Chem. 2015;290(37):22686–98.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Jain N, Mishra R, Ganesh S. FoxO3a-mediated autophagy is down-regulated in the laforin deficient mice, an animal model for Lafora progressive myoclonus epilepsy. Biochem Biophys Res Commun. 2016;474(2):321–7.CrossRefPubMedGoogle Scholar
  50. Jiang S, Wells CD, Roach PJ. Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1. Biochem Biophys Res Commun. 2011;413(3):420–5.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Kotting O, Santelia D, Edner C, Eicke S, Marthaler T, Gentry MS, et al. STARCH-EXCESS4 is a Laforin-like phosphoglucan phosphatase required for starch degradation in Arabidopsis thaliana. Plant Cell. 2009;21(1):334–46.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Lohi H, Ianzano L, Zhao X-C, Chan EM, Turnbull J, Scherer SW, et al. Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy. Hum Mol Genet. 2005;14(18):2727–36.CrossRefPubMedGoogle Scholar
  53. Lomako J, Lomako WM, Whelan WJ, Marchase RB. Glycogen contains phosphodiester groups that can be introduced by UDPglucose: glycogen glucose 1-phosphotransferase. FEBS Lett. 1993;329(3):263–7.CrossRefPubMedGoogle Scholar
  54. Lomako J, Lomako WM, Kirkman BR, Whelan WJ. The role of phosphate in muscle glycogen. Biofactors. 1994;4(3–4):167–71.Google Scholar
  55. Lopez-Gonzalez I, Viana R, Sanz P, Ferrer I. Inflammation in Lafora disease: evolution with disease progression in laforin and malin knock-out mouse models. Mol Neurobiol. 2016. [Epub ahead of print] DOI: 10.1007/s12035-016-9884-4.CrossRefPubMedPubMedCentralGoogle Scholar
  56. McBride A, Ghilagaber S, Nikolaev A, Hardie DG. The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor. Cell Metab. 2009;9(1):23–34.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Meekins DA, Raththagala M, Auger KD, Turner BD, Santelia D, Kotting O, et al. Mechanistic insights into glucan phosphatase activity against polyglucan substrates. J Biol Chem. 2015;290(38):23361–70.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Meekins DA, Vander Kooi CW, Gentry MS. Structural mechanisms of plant glucan phosphatases in starch metabolism. FEBS J. 2016;283(13):2427–47.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Minassian BA. Lafora’s disease: towards a clinical, pathologic, and molecular synthesis. Pediatr Neurol. 2001;25(1):21–9.CrossRefPubMedGoogle Scholar
  60. Minassian BA, Lee JR, Herbrick JA, Huizenga J, Soder S, Mungall AJ, et al. Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy. Nat Genet. 1998;20(2):171–4.CrossRefPubMedGoogle Scholar
  61. Minassian BA, Andrade DM, Ianzano L, Young EJ, Chan E, Ackerley CA, et al. Laforin is a cell membrane and endoplasmic reticulum-associated protein tyrosine phosphatase. Ann Neurol. 2001;49(2):271–5.CrossRefPubMedGoogle Scholar
  62. Mittal S, Dubey D, Yamakawa K, Ganesh S. Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment. Hum Mol Genet. 2007;16(7):753–62.CrossRefPubMedGoogle Scholar
  63. Mittal S, Upadhyay M, Singh PK, Parihar R, Ganesh S. Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease. J Biosci. 2015;40(5):863–71.CrossRefPubMedGoogle Scholar
  64. Munoz-Ballester C, Berthier A, Viana R, Sanz P. Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease. Biochim Biophys Acta. 2016;1862(6):1074–83.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Nitschke F, Wang P, Schmieder P, Girard JM, Awrey DE, Wang T, et al. Hyperphosphorylation of glucosyl c6 carbons and altered structure of glycogen in the neurodegenerative epilepsy lafora disease. Cell Metab. 2013;17(5):756–67.CrossRefGoogle Scholar
  66. Obel LF, Muller MS, Walls AB, Sickmann HM, Bak LK, Waagepetersen HS, et al. Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. Front Neuroenergeti. 2012;4:3.CrossRefGoogle Scholar
  67. Pederson BA, Turnbull J, Epp JR, Weaver SA, Zhao X, Pencea N, et al. Inhibiting glycogen synthesis prevents Lafora disease in a mouse model. Ann Neurol. 2013;74(2):297–300.PubMedPubMedCentralGoogle Scholar
  68. Pfister B, Zeeman SC. Formation of starch in plant cells. Cell Mol Life Sci. 2016;73(14):2781–807.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Puri R, Suzuki T, Yamakawa K, Ganesh S. Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease. J Biol Chem. 2009;284(34):22657–63.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Puri R, Suzuki T, Yamakawa K, Ganesh S. Dysfunctions in endosomal-lysosomal and autophagy pathways underlie neuropathology in a mouse model for Lafora disease. Hum Mol Genet. 2012;21(1):175–84.CrossRefPubMedGoogle Scholar
  71. Raththagala M, Brewer MK, Parker MW, Sherwood AR, Wong BK, Hsu S, et al. Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease. Mol Cell. 2015;57(2):261–72.CrossRefPubMedGoogle Scholar
  72. Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS. Glycogen and its metabolism: some new developments and old themes. Biochem J. 2012;441(3):763–87.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Roma-Mateo C, Solaz-Fuster Mdel C, Gimeno-Alcaniz JV, Dukhande VV, Donderis J, Worby CA, et al. Laforin, a dual-specificity phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase. Biochem J. 2011a;439(2):265–75.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Roma-Mateo C, Moreno D, Vernia S, Rubio T, Bridges TM, Gentry MS, et al. Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level. BMC Evol Biol. 2011b;11:225.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Roma-Mateo C, Aguado C, Garcia-Gimenez JL, Ibanez-Cabellos JS, Seco-Cervera M, Pallardo FV, et al. Increased oxidative stress and impaired antioxidant response in Lafora disease. Free Radic Biol Med. 2014;75(Suppl 1):S47.CrossRefPubMedGoogle Scholar
  76. Roma-Mateo C, Raththagala M, Gentry MS, Sanz P. Assessing the Biological Activity of the Glucan Phosphatase Laforin. Methods Mol Biol. 2016;1447:107–19.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Rubio-Villena C, Garcia-Gimeno MA, Sanz P. Glycogenic activity of R6, a protein phosphatase 1 regulatory subunit, is modulated by the laforin-malin complex. Int J Biochem Cell Biol. 2013;45(7):1479–88.CrossRefPubMedGoogle Scholar
  78. Saez I, Duran J, Sinadinos C, Beltran A, Yanes O, Tevy MF, et al. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia. J Cereb Blood Flow Metab. 2014;34(6):945–55.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Sakai M, Austin J, Witmer F, Trueb L. Studies in myoclonus epilepsy (Lafora body form). II. Polyglucosans in the systemic deposits of myoclonus epilepsy and in corpora amylacea. Neurology. 1970;20(2):160–76.CrossRefPubMedGoogle Scholar
  80. Sanchez-Martin P, Raththagala M, Bridges TM, Husodo S, Gentry MS, Sanz P, et al. Dimerization of the glucan phosphatase laforin requires the participation of cysteine 329. PLoS One. 2013;8(7):e69523.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Sanchez-Martin P, Roma-Mateo C, Viana R, Sanz P. Ubiquitin conjugating enzyme E2-N and sequestosome-1 (p62) are components of the ubiquitination process mediated by the malin-laforin E3-ubiquitin ligase complex. Int J Biochem Cell Biol. 2015;69:204–14.CrossRefPubMedGoogle Scholar
  82. Sankhala RS, Koksal AC, Ho L, Nitschke F, Minassian BA, Cingolani G. Dimeric quaternary structure of human laforin. J Biol Chem. 2014;290(8):4552–9.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Santelia D, Kotting O, Seung D, Schubert M, Thalmann M, Bischof S, et al. The phosphoglucan phosphatase like sex Four2 dephosphorylates starch at the C3-position in Arabidopsis. Plant Cell. 2011;23(11):4096–111.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Schnabel R, Seitelberger F. Histophysical and histochemical investigations of myoclonus bodies. Pathol Eur. 1968;3(2):218–26.PubMedGoogle Scholar
  85. Serratosa JM, Delgado-Escueta AV, Posada I, Shih S, Drury I, Berciano J, et al. The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q. Hum Mol Genet. 1995;4(9):1657–63.CrossRefPubMedGoogle Scholar
  86. Sherwood AR, Paasch BC, Worby CA, Gentry MS. A malachite green-based assay to assess glucan phosphatase activity. Anal Biochem. 2013;435(1):54–6.CrossRefPubMedGoogle Scholar
  87. Sickmann HM, Waagepetersen HS, Schousboe A, Benie AJ, Bouman SD. Brain glycogen and its role in supporting glutamate and GABA homeostasis in a type 2 diabetes rat model. Neurochem Int. 2012;60(3):267–75.CrossRefPubMedGoogle Scholar
  88. Silver DM, Kotting O, Moorhead GB. Phosphoglucan phosphatase function sheds light on starch degradation. Trends Plant Sci. 2014;19(7):471–8.CrossRefPubMedGoogle Scholar
  89. Singh PK, Singh S, Ganesh S. The laforin-malin complex negatively regulates glycogen synthesis by modulating cellular glucose uptake via glucose transporters. Mol Cell Biol. 2012;32(3):652–63.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Smirnova J, Fernie AR, Steup M. Starch degradation. In: Starch: metabolism and structure. Tokyo: Springer; 2015. p. 239–90.CrossRefGoogle Scholar
  91. Swanson RA, Yu AC, Chan PH, Sharp FR. Glutamate increases glycogen content and reduces glucose utilization in primary astrocyte culture. J Neurochem. 1990;54(2):490–6.CrossRefPubMedGoogle Scholar
  92. Tagliabracci VS, Turnbull J, Wang W, Girard JM, Zhao X, Skurat AV, et al. Laforin is a glycogen phosphatase, deficiency of which leads to elevated phosphorylation of glycogen in vivo. Proc Natl Acad Sci USA. 2007;104(49):19262–6.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Tagliabracci VS, Girard JM, Segvich D, Meyer C, Turnbull J, Zhao X, et al. Abnormal metabolism of glycogen phosphate as a cause for lafora disease. J Biol Chem. 2008;283(49):33816–25.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Tagliabracci VS, Heiss C, Karthik C, Contreras CJ, Glushka J, Ishihara M, et al. Phosphate incorporation during glycogen synthesis and Lafora disease. Cell Metab. 2011;13(3):274–82.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Tiberia E, Turnbull J, Wang T, Ruggieri A, Zhao XC, Pencea N, et al. Increased laforin and laforin binding to glycogen underlie Lafora body formation in malin-deficient Lafora disease. J Biol Chem. 2012;287(30):25650–9.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Tonks NK. Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol. 2006;7(11):833–46.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Turnbull J, Depaoli-Roach AA, Zhao X, Cortez MA, Pencea N, Tiberia E, et al. PTG depletion removes Lafora bodies and rescues the fatal epilepsy of Lafora disease. PLoS Genet. 2011;7(4):e1002037.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Turnbull J, Epp JR, Goldsmith D, Zhao X, Pencea N, Wang P, et al. PTG protein depletion rescues malin-deficient Lafora disease in mouse. Ann Neurol. 2014;75(3):442–6.CrossRefPubMedGoogle Scholar
  99. Valles-Ortega J, Duran J, Garcia-Rocha M, Bosch C, Saez I, Pujadas L, et al. Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease. EMBO Mol Med. 2011;3(11):667–81.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Vernia S, Solaz-Fuster MC, Gimeno-Alcaniz JV, Rubio T, Garcia-Haro L, Foretz M, et al. AMP-activated protein kinase phosphorylates R5/PTG, the glycogen targeting subunt of the R5/PTG-PP1 holoenzyme and accelerates its downregulation by the laforin-malin complex. J Biol Chem. 2009;284(13):8247–55.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Viana R, Lujan P, Sanz P. The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2. BMC Biochem. 2015;16:24.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Vilchez D, Ros S, Cifuentes D, Pujadas L, Valles J, Garcia-Fojeda B, et al. Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat Neurosci. 2007;10(11):1407–13.CrossRefPubMedGoogle Scholar
  103. Wang W, Roach PJ. Glycogen and related polysaccharides inhibit the laforin dual-specificity protein phosphatase. Biochem Biophys Res Commun. 2004;325(3):726–30.CrossRefPubMedGoogle Scholar
  104. Wang J, Stuckey JA, Wishart MJ, Dixon JE. A unique carbohydrate binding domain targets the lafora disease phosphatase to glycogen. J Biol Chem. 2002;277(4):2377–80.CrossRefPubMedGoogle Scholar
  105. Wang W, Parker GE, Skurat AV, Raben N, DePaoli-Roach AA, Roach PJ. Relationship between glycogen accumulation and the laforin dual specificity phosphatase. Biochem Biophys Res Commun. 2006a;350(3):588–92.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Wang Y, Liu Y, Wu C, Zhang H, Zheng X, Zheng Z, et al. Epm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt signaling. Cancer Cell. 2006b;10(3):179–90.CrossRefPubMedGoogle Scholar
  107. Wang W, Lohi H, Skurat AV, Depaoli-Roach AA, Minassian BA, Roach PJ. Glycogen metabolism in tissues from a mouse model of Lafora disease. Arch Biochem Biophys. 2007;457(2):264–9.CrossRefPubMedGoogle Scholar
  108. Worby CA, Gentry MS, Dixon JE. Laforin: a dual specificity phosphatase that dephosphorylates complex carbohydrates. J Biol Chem. 2006;281(41):30412–8.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Worby CA, Gentry MS, Dixon JE. Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG). J Biol Chem. 2008;283(7):4069–76.CrossRefPubMedGoogle Scholar
  110. Yokoi S, Austin J, Witmer F, Sakai M. Studies in myoclonus epilepsy (Lafora body form). I. Isolation and preliminary characterization of Lafora bodies in two cases. Arch Neurol. 1968;19(1):15–33.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • M. Kathryn Brewer
    • 1
  • Amanda R. Sherwood
    • 1
  • Vikas V. Dukhande
    • 2
  • Matthew S. Gentry
    • 1
  1. 1.Department of Molecular and Cellular BiochemistryUniversity of Kentucky College of MedicineLexingtonUSA
  2. 2.Department of Pharmaceutical Sciences, College of Pharmacy and Health SciencesSt. John’s UniversityJamaicaUSA