Utilizing Red Algae to Understand a Neurodegenerative Disease

  • Matthew S. GentryEmail author
  • Seema Mattoo
  • Jack E. Dixon
Part of the Cellular Origin, Life in Extreme Habitats and Astrobiology book series (COLE, volume 13)


Mutations in the gene encoding the dual specificity phosphatase laforin result in Lafora disease (LD), a neurodegenerative disease that causes epilepsy and death. A hallmark of LD is the accumulation of insoluble carbohydrate bodies, called Lafora bodies (LBs), in the cytoplasm of cells of LD patients. Some protists, notably the red alga Cyanidioschyzon merolae, synthesize a type of insoluble carbohydrate called floridean starch in their cytoplasm that appears similar in composition to the LBs. We recently identified, cloned, purified, and characterized an ortholog of human laforin from C. merolae and demonstrated that C. merolae laforin has similar properties as the human laforin. In this chapter, we will discuss this finding and how a red alga can contribute to our knowledge and understanding of the molecular mechanism(s) that causes LD.


Lafora disease, LD Lafora bodies, LB malin laforin phosphatase DSP CBM floridean starch C. merolae chromalveolate SEX4 


  1. Acharya, J.N., Satishchandra, P. and Shankar, S.K. (1995) Familial progressive myoclonus epilepsy: clinical and electrophysiologic observations. Epilepsia 36: 429–434.PubMedCrossRefGoogle Scholar
  2. Allen, M.B. (1959) Studies with cyanidium caldarium, an anomalously pigmented chlorophyte. Arch. Microbiol. 32: 270.Google Scholar
  3. Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Friedberg, I., Osterman, A., Godzik, A., Hunter, T., Dixon, J. and Mustelin, T. (2004) Protein tyrosine phosphatases in the human genome. Cell 117: 699.PubMedCrossRefGoogle Scholar
  4. Ball, S.G. and Morell, M.K. (2003) From bacterial glycogen to starch: understanding the biogenesis of the plant starch granule. Annu. Rev. Plant Biol. 54: 207–233.CrossRefGoogle Scholar
  5. Barbier, G., Oesterhelt, C., Larson, M.D., Halgren, R.G., Wilkerson, C., Garavito, R.M., Benning, C. and Weber, A.P.M. (2005) Comparative genomics of two closely related unicellular thermo-acidophilic red algae, Galdieria sulphuraria and Cyanidioschyzon merolae, reveals the molecular basis of the metabolic flexibility of Galdieria sulphuraria and significant differences in carbohydrate metabolism of both algae. Plant Physiol. 137: 460–474.PubMedCrossRefGoogle Scholar
  6. Bateman, A., Coin, L., Durbin, R., Finn, R.D., Hollich, V., Griffiths-Jones, S., Khanna, A., Marshall, M., Moxon, S., Sonnhammer, E.L.L., Studholme, D.J., Yeats, C. and Eddy, S.R. (2004) The Pfam protein families database. Nucl. Acids Res. 32: D138–D141.PubMedCrossRefGoogle Scholar
  7. Baunsgaard, L., Lutken, H., Mikkelsen, R., Glaring, M.A., Pham, T.T. and Blennow, A. (2005) A novel isoform of glucan, water dikinase phosphorylates pre-phosphorylated alpha-glucans and is involved in starch degradation in Arabidopsis. Plant J. 41: 595–605.PubMedCrossRefGoogle Scholar
  8. Berkovic, S.F., Andermann, F., Carpenter, S. and Wolfe, L.S. (1986) Progressive myoclonus epilepsies: specific causes and diagnosis. N. Engl. J. Med. 315: 296–305.PubMedCrossRefGoogle Scholar
  9. Berkovic, S.F., Cochius, J., Andermann, E. and Andermann, F. (1993) Progressive myoclonus epilepsies: clinical and genetic aspects. Epilepsia 34(Suppl 3): S19–S30.PubMedGoogle Scholar
  10. Berkovic, S.F., So, N.K. and Andermann, F. (1991) Progressive myoclonus epilepsies: clinical and neurophysiological diagnosis. J. Clin. Neurophysiol. 8: 261–274.PubMedCrossRefGoogle Scholar
  11. Bhattacharya, D. and Medlin, L. (1998) Algal phylogeny and the origin of land plants. Plant Physiol. 116: 9–15.CrossRefGoogle Scholar
  12. Blennow, A., Nielsen, T.H., Baunsgaard, L., Mikkelsen, R. and Engelsen, S.B. (2002) Starch phosphorylation: a new front line in starch research. Trends Plant Sci. 7: 445–450.PubMedCrossRefGoogle Scholar
  13. Boraston, A.B., Bolam, D.N., Gilbert, H.J. and Daview, G.J. (2004) Carbohydrate-binding modules: fine-tuning polysaccharide recognition. Biochem. J. 382: 769–781.PubMedCrossRefGoogle Scholar
  14. Carpenter, S. and Karpati, G. (1981) Sweat gland duct cells in Lafora disease: diagnosis by skin biopsy. Neurology 31: 1564–1568.PubMedCrossRefGoogle Scholar
  15. Cavalier-Smith, T. (1982) The origin of plastids. Biol. J. Linn. Soc. 17: 289–306.CrossRefGoogle Scholar
  16. Cavalier-Smith, T. (1999) Principles of protein and lipid targeting in secondary symbiogenesis: euglenoid, dinoflagellatae, and sporozoan plastid origins and the eukaryote family tree. J. Eukaryot. Microbiol. 46: 347–366.PubMedCrossRefGoogle Scholar
  17. Cavalier-Smith, T. (2004) Only six kingdoms of life. Proc. Biol. Sci. 271: 1251–1262.PubMedCrossRefGoogle Scholar
  18. Chan, E.M., Ackerley, C.A., Lohi, H., Ianzano, L., Cortez, M.A., Shannon, P., Scherer, S.W. and Minassian, B.A. (2004) Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy. Hum. Mol. Genet. 13: 1117–1129.PubMedCrossRefGoogle Scholar
  19. Chan, E.M., Young, E.J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C.C., Avanzini, G., Elia, M., Ackerley, C.A., Jovic, N.J., Bohlega, S., Andermann, E., Rouleau, G.A., Delgado-Escueta, A.V., Minassian, B.A. and Scherer, S.W. (2003) Mutations in NHLRC1 cause progressive myoclonus epilepsy. Nat. Genet. 35: 125–127.PubMedCrossRefGoogle Scholar
  20. Coppin, A., Dzierszinski, F., Legrand, S., Mortuaire, M., Ferguson, D. and Tomavo, S. (2003) Developmentally regulated biosynthesis of carbohydrate and storage polysaccharide during differentiation and tissue cyst formation in Toxoplasma gondii. Biochimie 85: 353.PubMedCrossRefGoogle Scholar
  21. Coppin, A., Varré, J., Lienard, L., Dauvillée, D., Guérardel, Y., Soyer-Gobillard, M., Buléon, A., Ball, S. and Tomavo, S. (2005) Evolution of plant-like crystalline storage polysaccharide in the protozoan parasite Toxoplasma gondii argues for a red alga ancestry. J. Mol. Evol. 60: 257–267.PubMedCrossRefGoogle Scholar
  22. Coutinho, P.M. and Henrissat, B. (1999) Carbohydrate-active enzymes: an integrated database approach, In: G.D. H.J. Gilbert, B. Henrissat and B. Svensson (eds.) Recent Advances in Carbohydrate Bioengineering. The Royal Society of Chemistry, Cambridge, pp. 3–12.Google Scholar
  23. Dubey, J.P. and Frenkel, J.K. (1972) Cyst-induced toxoplasmosis in cats. J. Protozool. 19: 155.PubMedGoogle Scholar
  24. Edner, C., Li, J., Albrecht, T., Mahlow, S., Hejazi, M., Hussain, H., Kaplan, F., Guy, C., Smith, S.M., Steup, M. and Ritte, G. (2007) Glucan, water dikinase activity stimulates breakdown of starch granules by plastidial beta-amylases. Plant Physiol. 145: 17–28.PubMedCrossRefGoogle Scholar
  25. Edwards, T.A., Wilkinson, B.D., Wharton, R.P. and Aggarwal, A.K. (2003) Model of the brain tumor-Pumilio translation repressor complex. Genes Dev. 17: 2508–2513.PubMedCrossRefGoogle Scholar
  26. Ekman, P., Yu, S.K. and Pedersén, M. (1991) Effects of altered salinity, darkness and algal nutrient status on floridoside and starch content, alpha-galactosidase activity and agar yield of cultivated Gracilaria sordida. Br. Phycol. J. 26: 123–131.CrossRefGoogle Scholar
  27. Embley, T.M. and Martin, W. (2006) Eukaryotic evolution, changes and challenges. Nature 440: 623–630.PubMedCrossRefGoogle Scholar
  28. Fordham-Skelton, A.P., Chilley, P., Lumbreras, V., Reignoux, S., Fenton, T.R., Dahm, C.C., Pages, M. and Gatehouse, J.A. (2002) A novel higher plant protein tyrosine phosphatase interacts with SNF1-related protein kinases via a KIS (kinase interaction sequence) domain. Plant J. 29: 705–715.PubMedCrossRefGoogle Scholar
  29. Ganesh, S., Agarwala, K.L., Amano, K., Suzuki, T., Delgado-Escueta, A.V. and Yamakawa, K. (2001) Regional and developmental expression of Epm2a gene and its evolutionary conservation. Biochem. Biophys. Res. Commun. 283: 1046–1053.PubMedCrossRefGoogle Scholar
  30. Ganesh, S., Agarwala, K.L., Ueda, K., Akagi, T., Shoda, K., Usui, T., Hashikawa, T., Osada, H., Delgado-Escueta, A.V. and Yamakawa, K. (2000) Laforin, defective in the progressive myoclonus epilepsy of Lafora type, is a dual-specificity phosphatase associated with polyribosomes. Hum. Mol. Genet. 9: 2251–2261.PubMedCrossRefGoogle Scholar
  31. Ganesh, S., Delgado-Escueta, A.V., Sakamoto, T., Avila, M.R., Machado-Salas, J., Hoshii, Y., Akagi, T., Gomi, H., Suzuki, T., Amano, K., Agarwala, K.L., Hasegawa, Y., Bai, D.S., Ishihara, T., Hashikawa, T., Itohara, S., Cornford, E.M., Niki, H. and Yamakawa, K. (2002) Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice. Hum. Mol. Genet. 11: 1251–1262.PubMedCrossRefGoogle Scholar
  32. Ganesh, S., Tsurutani, N., Suzuki, T., Hoshii, Y., Ishihara, T., Delgado-Escueta, A.V. and Yamakawa, K. (2004) The carbohydrate-binding domain of Lafora disease protein targets Lafora polyglucosan bodies. Biochem. Biophys. Res. Commun. 313: 1101–1109.PubMedCrossRefGoogle Scholar
  33. Gentry, M.S., Dowen, R.H. 3rd, Worby, C.A., Mattoo, S., Ecker, J.R. and Dixon, J.E. (2007) The phosphatase laforin crosses evolutionary boundaries and links carbohydrate metabolism to neuronal disease. J. Cell Biol. 178: 477–488.PubMedCrossRefGoogle Scholar
  34. Gentry, M.S., Worby, C.A. and Dixon, J.E. (2005) Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin. Proc. Natl. Acad. Sci. USA. 102: 8501–8506.PubMedCrossRefGoogle Scholar
  35. Gillott, M.A. and Gibbs, S.P. (1980) The cryptomonad nucleomorth: its ultrastructure and evolutionary significance. J. Phycol. 16: 558–568.CrossRefGoogle Scholar
  36. Guérardel, Y., Leleu, D., Coppin, A., Liénard, L., Slomianny, C., Strecker, G., Ball, S. and Tomavo, S. (2005) Amylopectin biogenesis and characterization in the protozoan parasite Toxoplasma gondii, the intracellular development of which is restricted in the HepG2 cell line. Microbes Infect. 7: 41–48.PubMedCrossRefGoogle Scholar
  37. Harriman, D.G., Millar, J.H. and Stevenson, A.C. (1955) Progressive familial myoclonic epilepsy in three families: its clinical features and pathological basis. Brain 78: 325–349.PubMedCrossRefGoogle Scholar
  38. Hershko, A. and Ciechanover, A. (1998) The ubiquitin system. Annu. Rev. Biochem. 67: 425–479.PubMedCrossRefGoogle Scholar
  39. Hodskins, M.B. and Yakovlev, P.I. (1930) Anatomico-clinical observations on myclonus in epileptics and on related symptom complexes. Am. J. Psychiatry 86: 827–848.Google Scholar
  40. Ianzano, L., Zhang, J., Chan, E.M., Zhao, X., Lohi, H., Scherer, S.W. and Minassian, B.A. (2005) Lafora progressive myoclonus epilepsy mutation database-EPM2A and NHLRC1 (EMP2B) genes. Hum. Mutat. 26: 397.PubMedCrossRefGoogle Scholar
  41. Itoh, R., Takahashi, H., Toda, K., Kuroiwa, H. and Kuroiwa, T. (1996) Aphidicolin uncouples the chloroplast division cycle from the mitotic cycle in the unicellular red alga Cyanidioschyzon merolae. Eur. J. Cell Biol. 71: 303–310.PubMedGoogle Scholar
  42. Janeway, R., Ravens, J.R., Pearce, L.A., Odor, D.L. and Suzuki, K. (1967) Progressive myoclonus epilepsy with Lafora inclusion bodies. I. Clinical, genetic, histopathologic, and biochemical aspects. Arch. Neurol. 16: 565–582.PubMedCrossRefGoogle Scholar
  43. Kerk, D., Conley, T.R., Rodriguez, F.A., Tran, H.T., Nimick, M., Muench, D.G. and Moorhead, G.B. (2006) A chloroplast-localized dual-specificity protein phosphatase in Arabidopsis contains a phylogenetically dispersed and ancient carbohydrate-binding domain, which binds the polysaccharide starch. Plant J. 46: 400–413.PubMedCrossRefGoogle Scholar
  44. Kotting, O., Pusch, K., Tiessen, A., Geigenberger, P., Steup, M. and Ritte, G. (2005) Identification of a novel enzyme required for starch metabolism in Arabidopsis leaves. The phosphoglucan, water dikinase. Plant Physiol. 137: 242–252.PubMedCrossRefGoogle Scholar
  45. Lafora, G.R. (1911) Uber des Vorkommen amyloider KJrperchen im innern der Ganglienzellen. Virchows Arch. f. Path. Anat. 205: 295.Google Scholar
  46. Lafora, G.R. and Gluck, B. (1911) Beitrag zur histopathologie der myoklonischen epilepsie. Z. Ges. Neurol. Psychiatry 6: 1–14.CrossRefGoogle Scholar
  47. Lomako, J., Lomako, W.M., Kirkman, B.R. and Whelan, W.J. (1994) The role of phosphate in muscle glycogen. Biofactors 4: 167–171.PubMedGoogle Scholar
  48. Lomako, J., Lomako, W.M., Whelan, W.J. and Marchase, R.B. (1993) Glycogen contains phosphodiester groups that can be introduced by UDPglucose: glycogen glucose 1-phosphotransferase. FEBS Lett. 329: 263–267.PubMedCrossRefGoogle Scholar
  49. Marchler-Bauer, A., Anderson, J.B., Cherukuri, P.F., DeWeese-Scott, C., Geer, L.Y., Gwadz, M., He, S., Hurwitz, D.I., Jackson, J.D., Ke, Z., Lanczycki, C.J., Liebert, C.A., Liu, C., Lu, F., Marchler, G.H., Mullokandov, M., Shoemaker, B.A., Simonyan, V., Song, J.S., Thiessen, P.A., Yamashita, R.A., Yin, J.J., Zhang, D. and Bryant, S.H. (2005) CDD: a conserved domain database for protein classification. Nucl. Acids Res. 33: D192–D196.PubMedCrossRefGoogle Scholar
  50. Matsuzaki, M., Misumi, O., Shin-i, T., Maruyama, S., Takahara, M. et al. (2004) Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428: 653–657.PubMedCrossRefGoogle Scholar
  51. Meeuse, B.J.D., Andries, M. and Wood, J.A. (1960) Floridean Starch. J. Exp. Bot. 11: 129–140.CrossRefGoogle Scholar
  52. Minassian, B.A. (2001) Lafora’s disease: towards a clinical, pathologic, and molecular synthesis. Pediatr. Neurol. 25: 21–29.PubMedCrossRefGoogle Scholar
  53. Minassian, B.A., Lee, J.R., Herbrick, J.A., Huizenga, J., Soder, S., Mungall, A.J., Dunham, I., Gardner, R., Fong, C.Y., Carpenter, S., Jardim, L., Satishchandra, P., Andermann, E., Snead, O.C. 3rd, Lopes-Cendes, I., Tsui, L.C., Delgado-Escueta, A.V., Rouleau, G.A. and Scherer, S.W. (1998) Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy. Nat. Genet. 20: 171–174.PubMedCrossRefGoogle Scholar
  54. Minoda, A., Sakagami, R., Yagisawa, F., Kuroiwa, T. and Tanaka, K. (2004) Improvement of culture conditions and evidence for nuclear transformation by homologous recombination in a red alga, Cyanidioschyzon merolae 10D. Plant Cell Physiol. 45: 667–671.PubMedCrossRefGoogle Scholar
  55. Misumi, O., Matsuzaki, M., Nozaki, H., Miyagishima, S-y., Mori, T., Nishida, K., Yagisawa, F., Yoshida, Y., Kuroiwa, H. and Kuroiwa, T. (2005) Cyanidioschyzon merolae Genome. A tool for facilitating comparable studies on organelle biogenesis in photosynthetic eukaryotes. Plant Physiol. 137: 567–585.PubMedCrossRefGoogle Scholar
  56. Misumi, O., Yoshida, Y., Nishida, K., Fujiwara, T., Sakajiri, T., Hirooka, S., Nishimura, Y. and Kuroiwa, T. (2008) Genome analysis and its significance in four unicellular algae, Cyanidioshyzon merolae, Ostreococcus tauri, Chlamydomonas reinhardtii, and Thalassiosira pseudonana. J. Plant Res. 121: 3–17.PubMedCrossRefGoogle Scholar
  57. Miyagishima, S-y., Itoh, R., Aita, S., Kuroiwa, H. and Kuroiwa, T. (1999) Isolation of dividing chloroplasts with intact plastid-dividing rings from a synchronous culture of the unicellular red alga Cyanidioschyzon merolae. Planta 209: 371.PubMedCrossRefGoogle Scholar
  58. Miyagishima, S.-y., Itoh, R., Toda, K., Takahashi, H., Kuroiwa, H. and Kuroiwa, T. (1998) Orderly formation of the double ring structures for plastid and mitochondrial division in the unicellular red alga Cyanidioschyzon merolae. Planta. 206: 551.CrossRefGoogle Scholar
  59. Miyagishima, S-y., Takahara, M., Mori, T., Kuroiwa, H., Higashiyama, T. and Kuroiwa, T. (2001) Plastid division is driven by a complex mechanism that involves differential transition of the bacterial and eukaryotic division rings. Plant Cell 13: 2257–2268.Google Scholar
  60. Miyagishima, S.Y., Nishida, K., Mori, T., Matsuzaki, M., Higashiyama, T., Kuroiwa, H. and Kuroiwa, T. (2003) A plant-specific dynamin-related protein forms a ring at the chloroplast division site. Plant Cell 15: 655–665.PubMedCrossRefGoogle Scholar
  61. Myers, A.M., Morell, M.K., James, M.G. and Ball, S.G. (2000) Recent progress toward understanding biosynthesis of the amylopectin crystal. Plant Physiol. 122: 989–998.PubMedCrossRefGoogle Scholar
  62. Niittyla, T., S. Comparot-Moss, W.-L. Lue, G. Messerli, M. Trevisan, M.D.J. Seymour, J.A. Gatehouse, D. Villadsen, S.M. Smith, J. Chen, S.C. Zeeman, and Smith, A.M. (2006) Similar protein phosphatases control starch metabolism in plants and glycogen metabolism in mammals. J. Biol. Chem. 281: 11815–11818.PubMedCrossRefGoogle Scholar
  63. Nishida, K., Takahara, M., Miyagishima, S.-y., Kuroiwa, H., Matsuzaki, M. and Kuroiwa, T. (2003) Dynamic recruitment of dynamin for final mitochondrial severance in a primitive red alga. PNAS 100: 2146–2151.PubMedCrossRefGoogle Scholar
  64. Nishida, K., Yagisawa, F., Kuroiwa, H., Nagata, T. and Kuroiwa, T. (2005) Cell cycle-regulated, microtubule-independent organelle division in Cyanidioschyzon merolae. Mol. Biol. Cell 16: 2493–2502.PubMedCrossRefGoogle Scholar
  65. Nyvall, P., Pelloux, P., Davies, H.V., Pedersen, M. and Roberto, V. (1999) Purification and characterisation of a novel starch synthase selective for uridine 5´-diphosphate glucose from the red alga Gracilaria tenuistipitata. Planta 209: 143–152.PubMedCrossRefGoogle Scholar
  66. Ohnuma, M., Yokoyama, T., Inouye, T., Sekine, Y. and Tanaka, K. (2008) Polyethylene glycol (PEG)-mediated transient gene expression in a red alga, Cyanidioschyzon merolae 10D. Plant Cell Physiol. 49(1): 117–120.CrossRefGoogle Scholar
  67. Ohta, N., Sato, N., Kawano, S. and Kuroiwa, T. (1994) The trpA gene on the plastid genome of Cyanidium caldarium strain RK-1. Curr. Genet. 25: 357.PubMedCrossRefGoogle Scholar
  68. Pickart, C.M. (2001) Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70: 503–533.PubMedCrossRefGoogle Scholar
  69. Ritte, G., Heydenreich, M., Mahlow, S., Haebel, S., Kotting, O. and Steup, M. (2006) Phosphorylation of C6- and C3-positions of glucosyl residues in starch is catalysed by distinct dikinases. FEBS Lett. 580: 4872–4876.PubMedCrossRefGoogle Scholar
  70. Ritte, G., Lloyd, J.R., Eckermann, N., Rottmann, A., Kossmann, J. and Steup, M. (2002) The starch-related R1 protein is an alpha-glucan, water dikinase. Proc. Natl. Acad. Sci. USA 99: 7166–7171.PubMedCrossRefGoogle Scholar
  71. Rodriguez-Sanoja, R., Oviedo, N. and Sanchez, S. (2005) Microbial starch-binding domain. Curr. Opin. Microbiol. 8: 260–267.PubMedCrossRefGoogle Scholar
  72. Sakai, M., Austin, J., Witmer, F. and Trueb, L. (1970) Studies in myoclonus epilepsy (Lafora body form). II. Polyglucosans in the systemic deposits of myoclonus epilepsy and in corpora amylacea. Neurology 20: 160–176.PubMedCrossRefGoogle Scholar
  73. Schnabel, R. and Seitelberger, F. (1968) Histophysical and histochemical investigations of myoclonus bodies. Pathol. Eur. 3: 218–226.PubMedGoogle Scholar
  74. Schwarz, G.A. and Yanoff, M. (1965) Lafora’s disease. Distinct clinico-pathologic form of Unverricht’s syndrome. Arch. Neurol. 12: 172–188.PubMedCrossRefGoogle Scholar
  75. Serratosa, J.M., Gomez-Garre, P., Gallardo, M.E., Anta, B., de Bernabe, D.B., Lindhout, D., Augustijn, P.B., Tassinari, C.A., Malafosse, R.M., Topcu, M., Grid, D., Dravet, C., Berkovic, S.F. and de Cordoba, S.R. (1999) A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). Hum. Mol. Genet. 8: 345–352.PubMedCrossRefGoogle Scholar
  76. Sesma, J.I. and Iglesias, A.A. (1998) Synthesis of floridean starch in the red alga Gracilariz gracilis occurs via ADPglucose, In: G. Garab (ed.) Photosynthesis: Mechanisms and Effects. Vol. V. Kluwer, Dordrecht, The Netherlands, pp. 3537–3540.Google Scholar
  77. Slack, F.J. and Ruvkun, G. (1998) A novel repeat domain that is often associated with RING finger and B-box motifs. Trends Biochem. Sci. 23: 474–475.PubMedCrossRefGoogle Scholar
  78. Smith, A.M., Zeeman, S.C. and Smith, S.M. (2005) Starch degradation. Annu. Rev. Plant Biol. 56: 73–98.PubMedCrossRefGoogle Scholar
  79. Smith, S.M., Fulton, D.C., Chia, T., Thorneycroft, D., Chapple, A., Dunstan, H., Hylton, C., Zeeman, S.C. and Smith, A.M. (2004) Diurnal changes in the transcriptome encoding enzymes of starch metabolism provide evidence for both transcriptional and posttranscriptional regulation of starch metabolism in Arabidopsis leaves. Plant Physiol. 136: 2687–2699.PubMedCrossRefGoogle Scholar
  80. Sokolov, L.N., Dominguez-Solis, J.R., Allary, A.L., Buchanan, B.B. and Luan, S. (2006) A redox-regulated chloroplast protein phosphatase binds to starch diurnally and functions in its accumulation. Proc. Natl. Acad. Sci. USA 103: 9732–9737.PubMedCrossRefGoogle Scholar
  81. Solaz-Fuster, M.D., Gimeno-Alcaniz, J.V., Ros, S., Fernandez-Sanchez, M.E., Garcia-Fojeda, B., Garcia, O.C., Vilchez, D., Dominguez, J., Garcia-Rocha, M., Sanchez-Piris, M., Aguado, C., Knecht, E., Serratosa, J., Guinovart, J.J., Sanz, P. and de Cordoba, S.R. (2008) Regulation of glycogen synthesis by the laforin–malin complex is modulated by the AMP-activated protein kinase pathway. Hum. Mol. Genet. 17(5): 667–678.PubMedCrossRefGoogle Scholar
  82. Takahara, M., Takahashi, H., Matsunaga, S., Miyagishima, S., Takano, H., Sakai, A., Kawano, S. and Kuroiwa, T. (2000) A putative mitochondrial ftsZ gene is present in the unicellular primitive red alga Cyanidioschyzon merolae. Mol. Gen. Genomics 264: 452.CrossRefGoogle Scholar
  83. Van Heycop Ten Ham, M.W. (1974) Lafora disease, a form of progressive myoclonus epilepsy, In: P.J. Vinken and G.W. Bruyn (eds.) Handbook of Clinical Neurology. Vol. 15: In: O. Magnus and A.M. Lorentz de Haas (eds.) The Epilepsies. North Holland Publ. Comp., Amsterdam, p. 860.Google Scholar
  84. Vilchez, D., Ros, S., Cifuentes, D., Pujadas, L., Valles, J., Garcia-Fojeda, B., Criado-Garcia, O., Fernandez-Sanchez, E., Medrano-Fernandez, I., Dominguez, J., Garcia-Rocha, M., Soriano, E., Rodriguez de Cordoba, S. and Guinovart, J.J. (2007) Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat. Neurosci. 10: 1407–1413.PubMedCrossRefGoogle Scholar
  85. Viola, R., Nyvall, P. and Pedersén, M. (2001) The unique features of starch metabolism in red algae. Proc. R. Soc. Lond. B. 268: 1417–1422.CrossRefGoogle Scholar
  86. Wang, J., Stuckey, J.A., Wishart, M.J. and Dixon, J.E. (2002) A unique carbohydrate binding domain targets the Lafora disease phosphatase to glycogen. J. Biol. Chem. 277: 2377–2380.PubMedCrossRefGoogle Scholar
  87. Wang, W., Parker, G.E., Skurat, A.V., Raben, N., DePaoli-Roach, A.A. and Roach, P.J. (2006) Relationship between glycogen accumulation and the laforin dual specificity phosphatase. Biochem. Biophys. Res. Commun. 350: 588–592.PubMedCrossRefGoogle Scholar
  88. Worby, C.A., Gentry, M.S. and Dixon, J.E. (2006) Laforin: a dual specificity phosphatase that dephosphorylates complex carbohydrates. J. Biol. Chem. 281: 30412–30418.PubMedCrossRefGoogle Scholar
  89. Worby, C.A., Gentry, M.S. and Dixon, J.E. (2008) Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG). J. Biol. Chem. 283(7): 4069–4076.PubMedCrossRefGoogle Scholar
  90. Yagisawa, F., Nishida, K., Okano, Y., Minoda, A., Tanaka, K. and Kuroiwa, T. (2004) Isolation of Cycloheximide-resistant mutants of Cyanidioschyzon merolae. Cytologia 69: 97–100.CrossRefGoogle Scholar
  91. Yokoi, S., Austin, J. and Witmer, F. (1967) Isolation and characterization of Lafora bodies in two cases of myoclonus epilepsy. J. Neuropathol. Exp. Neurol. 26: 125–127.PubMedGoogle Scholar
  92. Yokoi, S., Austin, J., Witmer, F. and Sakai, M. (1968) Studies in myoclonus epilepsy (Lafora body form). I. Isolation and preliminary characterization of Lafora bodies in two cases. Arch. Neurol. 19: 15–33.PubMedCrossRefGoogle Scholar
  93. Yu, T.-S., Zeeman, S.C., Thorneycroft, D., Fulton, D.C., Dunstan, H., Lue, W.-L., Hegemann, B., Tung, S.-Y., Umemoto, T., Chapple, A., Tsai, D.-L., Wang, S.-M., Smith, A.M., Chen, J. and Smith, S.M. (2005) {alpha}-Amylase is not required for breakdown of transitory starch in Arabidopsis leaves. J. Biol. Chem. 280: 9773–9779.PubMedCrossRefGoogle Scholar
  94. Yu, T.S., Kofler, H., Hausler, R.E., Hille, D., Flugge, U.I., Zeeman, S.C., Smith, A.M., Kossmann, J., Lloyd, J., Ritte, G., Steup, M., Lue, W.L., Chen, J. and Weber, A. (2001) The Arabidopsis sex1 mutant is defective in the R1 protein, a general regulator of starch degradation in plants, and not in the chloroplast hexose transporter. Plant Cell. 13: 1907–1918.PubMedGoogle Scholar
  95. Zeeman, S.C., Smith, S.M. and Smith, A.M. (2007) The diurnal metabolism of leaf starch. Biochem. J. 401: 13–28.PubMedCrossRefGoogle Scholar
  96. Zeeman, S.C., Tiessen, A., Pilling, E., Kato, K.L., Donald, A.M. and Smith, A.M. (2002) Starch synthesis in Arabidopsis. Granule synthesis, composition, and structure. Plant Physiol. 129: 516–529.PubMedCrossRefGoogle Scholar
  97. Zolnierowicz, S. (2000) Type 2A protein phosphatase, the complex regulator of numerous signaling pathways. Biochem. Pharmacol. 60: 1225.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Matthew S. Gentry
    • 1
    Email author
  • Seema Mattoo
    • 2
  • Jack E. Dixon
    • 2
  1. 1.Department of Molecular and Cellular BiochemistryUniversity of KentuckyLexingtonUSA
  2. 2.Department of Pharmacology and The Howard Hughes Medical InstituteUniversity of California-San DiegoLa JollaUSA

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