Table of Contents Author Guidelines Submit a Manuscript
International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 352805, 11 pages
http://dx.doi.org/10.4061/2011/352805
Review Article

Functional Implications of Glycogen Synthase Kinase-3-Mediated Tau Phosphorylation

Department of Neuroscience (P037), MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

Received 15 April 2011; Accepted 6 May 2011

Academic Editor: Adam Cole

Copyright © 2011 Diane P. Hanger and Wendy Noble. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Goedert, “Tau protein and the neurofibrillary pathology of Alzheimer's disease,” Trends in Neurosciences, vol. 16, no. 11, pp. 460–465, 1993. View at Google Scholar · View at Scopus
  2. L. Buée, T. Bussière, V. Buee-Scherrer, A. Delacourte, and P. R. Hof, “Tau protein isoforms, phosphorylation and role in neurodegenerative disorders,” Brain Research Reviews, vol. 33, no. 1, pp. 95–130, 2000. View at Publisher · View at Google Scholar · View at Scopus
  3. C. Ballatore, V. M. Lee, and J. Q. Trojanowski, “Tau-mediated neurodegeneration in Alzheimer's disease and related disorders,” Nature Reviews Neuroscience, vol. 8, no. 9, pp. 663–672, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. T. F. Gendron and L. Petrucelli, “The role of tau in neurodegeneration,” Molecular Neurodegeneration, vol. 4, p. 13, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. C. Viereck, R. P. Tucker, and A. Matus, “The adult rat olfactory system expresses microtubule-associated proteins found in the developing brain,” Journal of Neuroscience, vol. 9, no. 10, pp. 3547–3557, 1989. View at Google Scholar · View at Scopus
  6. R. P. Tucker, “The roles of microtubule-associated proteins in brain morphogenesis: a review,” Brain Research Reviews, vol. 15, no. 2, pp. 101–120, 1990. View at Publisher · View at Google Scholar · View at Scopus
  7. D. P. Hanger, B. H. Anderton, and W. Noble, “Tau phosphorylation: the therapeutic challenge for neurodegenerative disease,” Trends in Molecular Medicine, vol. 15, no. 3, pp. 112–119, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. M. Hasegawa, “Biochemistry and molecular biology of tauopathies,” Neuropathology, vol. 26, no. 5, pp. 484–490, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Mitchinson and M. Kirschner, “Dynamic instability of microtubule growth,” Nature, vol. 312, no. 5991, pp. 237–242, 1984. View at Google Scholar · View at Scopus
  10. G. Lindwall and R. D. Cole, “Phosphorylation affects the ability of tau protein to promote microtubule assembly,” Journal of Biological Chemistry, vol. 259, no. 8, pp. 5301–5305, 1984. View at Google Scholar · View at Scopus
  11. D. N. Drechsel, A. A. Hyman, M. H. Cobb, and M. W. Kirschner, “Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau,” Molecular Biology of the Cell, vol. 3, no. 10, pp. 1141–1154, 1992. View at Google Scholar · View at Scopus
  12. C. K. Combs, P. D. Coleman, and M. K. O'Banion, “Developmental regulation and PKC dependence of Alzheimer's-type tau phosphorylations in cultured fetal rat hippocampal neurons,” Developmental Brain Research, vol. 107, no. 1, pp. 143–158, 1998. View at Publisher · View at Google Scholar · View at Scopus
  13. W. B. Pope, S. A. Enam, N. Bawa, B. E. Miller, H. A. Ghanbari, and W. L. Klein, “Phosphorylated tau epitope of Alzheimer's disease is coupled to axon development in the avian central nervous system,” Experimental Neurology, vol. 120, no. 1, pp. 106–113, 1993. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. I. Cuchillo-Ibáñez, A. Seereeram, H. L. Byers et al., “Phosphorylation of tau regulates its axonal transport by controlling its binding to kinesin,” The FASEB Journal, vol. 22, no. 9, pp. 3186–3195, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. E. Thies and E. M. Mandelkow, “Missorting of tau in neurons causes degeneration of synapses that can be rescued by the kinase MARK2/Par-1,” Journal of Neuroscience, vol. 27, no. 11, pp. 2896–2907, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. G. A. Morfini, M. Burns, L. I. Binder et al., “Axonal transport defects in neurodegenerative diseases,” Journal of Neuroscience, vol. 29, no. 41, pp. 12776–12786, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. L. M. Ittner, Y. D. Ke, F. Delerue et al., “Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models,” Cell, vol. 142, no. 3, pp. 387–397, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. A. M. Pooler, A. Usardi, C. J. Evans, K. L. Philpott, W. Noble, and D. P. Hanger, “Dynamic association of tau with neuronal membranes is regulated by phosphorylation,” Neurobiology of Aging. In press.
  19. A. M. Pooler and D. P. Hanger, “Functional implications of the association of tau with the plasma membrane,” Biochemical Society Transactions, vol. 38, no. 4, pp. 1012–1015, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. C. H. Reynolds, C. J. Garwood, S. Wray et al., “Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases,” Journal of Biological Chemistry, vol. 283, no. 26, pp. 18177–18186, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. S. C. Hwang, D. Y. Jhon, Y. S. Bae, J. H. Kim, and S. G. Rhee, “Activation of phospholipase C-gamma by the concerted action of tau proteins and arachidonic acid,” Journal of Biological Chemistry, vol. 271, no. 31, pp. 18342–18349, 1996. View at Publisher · View at Google Scholar · View at Scopus
  22. S. M. Jenkins and G. V. Johnson, “Tau complexes with phospholipase C-gamma in situ,” NeuroReport, vol. 9, no. 1, pp. 67–71, 1998. View at Google Scholar · View at Scopus
  23. P. A. Loomis, T. H. Howard, R. P. Castleberry, and L. I. Binder, “Identification of nuclear ç isoforms in human neuroblastoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 21, pp. 8422–8426, 1990. View at Google Scholar · View at Scopus
  24. V. C. Thurston, R. P. Zinkowski, and L. I. Binder, “Tau as a nucleolar protein in human nonneural cells in vitro and in vivo,” Chromosoma, vol. 105, no. 1, pp. 20–30, 1996. View at Publisher · View at Google Scholar · View at Scopus
  25. Y. Wang, P. A. Loomis, R. P. Zinkowski, and L. I. Binder, “A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau,” Journal of Cell Biology, vol. 121, no. 2, pp. 257–267, 1993. View at Google Scholar · View at Scopus
  26. D. C. Cross, J. P. Muñoz, P. Hernandez, and R. B. Maccioni, “Nuclear and cytoplasmic tau proteins from human nonneuronal cells share common structural and functional features with brain tau,” Journal of Cellular Biochemistry, vol. 78, no. 2, pp. 305–317, 2000. View at Google Scholar · View at Scopus
  27. M. K. Sjoberg, E. Shestakova, Z. Mansuroglu, R. B. Maccioni, and E. Bonnefoy, “Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization,” Journal of Cell Science, vol. 119, no. 10, pp. 2025–2034, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. R. M. Brady, R. P. Zinkowski, and L. I. Binder, “Presence of tau in isolated nuclei from human brain,” Neurobiology of Aging, vol. 16, no. 3, pp. 479–486, 1995. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Sultan, F. Nesslany, M. Violet et al., “Nuclear tau, a key player in neuronal DNA protection,” Journal of Biological Chemistry, vol. 286, no. 6, pp. 4566–4575, 2011. View at Google Scholar
  30. J. A. Greenwood and G. V. W. Johnson, “Localization and in situ phosphorylation state of nuclear tau,” Experimental Cell Research, vol. 220, no. 2, pp. 332–337, 1995. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. T. Kampers, P. Friedhoff, J. Biernat, E. M. Mandelkow, and E. Mandelkow, “RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments,” FEBS Letters, vol. 399, no. 3, pp. 344–349, 1996. View at Publisher · View at Google Scholar · View at Scopus
  32. W. Li, X. S. Wang, M. H. Qu, Y. Liu, and R. Q. He, “Human protein tau represses DNA replication in vitro,” Biochimica et Biophysica Acta, vol. 1726, no. 3, pp. 280–286, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. S. W. Leung, L. H. Apponi, O. E. Cornejo et al., “Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein,” Gene, vol. 439, no. 1-2, pp. 71–78, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. C. R. Guthrie, L. Greenup, J. B. Leverenz, and B. C. Kraemer, “MSUT2 is a determinant of susceptibility to tau neurotoxicity,” Human Molecular Genetics, vol. 20, no. 10, pp. 1989–1999, 2011. View at Google Scholar
  35. C. R. Guthrie, G. D. Schellenberg, and B. C. Kraemer, “SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans,” Human Molecular Genetics, vol. 18, no. 10, pp. 1825–1838, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. T. Lebouvier, T. M. Scales, R. Williamson et al., “The microtubule-associated protein tau is also phosphorylated on tyrosine,” Journal of Alzheimer's Disease, vol. 18, no. 1, pp. 1–9, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. T. M. Scales, P. Derkinderen, K. Y. Leung et al., “Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn,” Molecular Neurodegeneration, vol. 6, p. 12, 2011. View at Google Scholar
  38. J. R. Woodgett, “Molecular cloning and expression of glycogen synthase kinase-3/factor A,” The EMBO Journal, vol. 9, no. 8, pp. 2431–2438, 1990. View at Google Scholar · View at Scopus
  39. D. P. Hanger, K. Hughes, J. R. Woodgett, J. P. Brion, and B. H. Anderton, “Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase,” Neuroscience Letters, vol. 147, no. 1, pp. 58–62, 1992. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Wood-Kaczmar, M. Kraus, K. Ishiguro, K. L. Philpott, and P. R. Gordon-Weeks, “An alternatively spliced form of glycogen synthase kinase-3beta is targeted to growing neurites and growth cones,” Molecular and Cellular Neuroscience, vol. 42, no. 3, pp. 184–194, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. B. W. Doble, S. A. Patel, G. A. Wood, L. K. Kockeritz, and J. R. Woodgett, “Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines,” Developmental Cell, vol. 12, no. 6, pp. 957–971, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. L. T. Alon, S. Pietrokovski, S. Barkan et al., “Selective loss of glycogen synthase kinase-3alpha in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation,” FEBS Letters, vol. 585, no. 8, pp. 1158–1162, 2011. View at Google Scholar
  43. K. MacAulay, B. W. Doble, S. A. Patel et al., “Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism,” Cell Metabolism, vol. 6, no. 4, pp. 329–337, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. K. P. Hoeflich, J. Luo, E. A. Rubie, M. S. Tsao, O. Jin, and J. R. Woodgett, “Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation,” Nature, vol. 406, no. 6791, pp. 86–90, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. J. E. Forde and T. C. Dale, “Glycogen synthase kinase 3: a key regulator of cellular fate,” Cellular and Molecular Life Sciences, vol. 64, no. 15, pp. 1930–1944, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. S. Frame and P. Cohen, “GSK3 takes centre stage more than 20 years after its discovery,” Biochemical Journal, vol. 359, no. 1, pp. 1–16, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. F. Hernández, E. Langa, R. Cuadros, J. Avila, and N. Villanueva, “Regulation of GSK3 isoforms by phosphatases PP1 and PP2A,” Molecular and Cellular Biochemistry, vol. 344, no. 1-2, pp. 211–215, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. W. Qian, J. Shi, X. Yin et al., “PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta,” Journal of Alzheimer's Disease, vol. 19, no. 4, pp. 1221–1229, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. Y. Kim, Y. I. Lee, M. Seo et al., “Calcineurin dephosphorylates glycogen synthase kinase-3 beta at serine-9 in neuroblast-derived cells,” Journal of Neurochemistry, vol. 111, no. 2, pp. 344–354, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. P. Cohen, “The structure and regulation of protein phosphatases,” Annual Review of Biochemistry, vol. 58, pp. 453–508, 1989. View at Google Scholar · View at Scopus
  51. I. D'Souza and G. D. Schellenberg, “Determinants of 4-repeat tau expression. Coordination between enhancing and inhibitory splicing sequences for exon 10 inclusion,” Journal of Biological Chemistry, vol. 275, no. 23, pp. 17700–17709, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. F. Hernández, M. Perez, J. J. Lucas, A. M. Mata, R. Bhat, and J. Avila, “Glycogen synthase kinase-3 plays a crucial role in tau exon 10 splicing and intranuclear distribution of SC35. Implications for Alzheimer's disease,” Journal of Biological Chemistry, vol. 279, no. 5, pp. 3801–3806, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. A. Takashima, T. Honda, K. Yasutake et al., “Activation of tau protein kinase I/glycogen synthase kinase-3beta by amyloid beta peptide (25–35) enhances phosphorylation of tau in hippocampal neurons,” Neuroscience Research, vol. 31, no. 4, pp. 317–323, 1998. View at Publisher · View at Google Scholar · View at Scopus
  54. K. L. Chen, R. Y. Yuan, C. J. Hu, and C. Y. Hsu, “Amyloid-beta peptide alteration of tau exon-10 splicing via the GSK3beta-SC35 pathway,” Neurobiology of Disease, vol. 40, no. 2, pp. 378–385, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. K. Ishiguro, M. Takahashi, K. Tomizawa et al., “Tau protein kinase I converts normal tau protein into A68- like component of paired helical filaments,” Journal of Biological Chemistry, vol. 267, no. 15, pp. 10897–10901, 1992. View at Google Scholar · View at Scopus
  56. S. Lovestone, C. H. Reynolds, D. Latimer et al., “Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells,” Current Biology, vol. 4, no. 12, pp. 1077–1086, 1994. View at Google Scholar · View at Scopus
  57. R. Gómez-Sintes, F. Hernández, A. Bortolozzi et al., “Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice,” The EMBO Journal, vol. 26, no. 11, pp. 2743–2754, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. Z. Yuan, A. Agarwal-Mawal, and H. K. Paudel, “14-3-3 binds to and mediates phosphorylation of microtubule-associated tau protein by Ser9-phosphorylated glycogen synthase kinase 3beta in the brain,” Journal of Biological Chemistry, vol. 279, no. 25, pp. 26105–26114, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. A. Agarwal-Mawal, H. Y. Qureshi, P. W. Cafferty et al., “14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex,” Journal of Biological Chemistry, vol. 278, no. 15, pp. 12722–12728, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. D. P. Hanger, H. L. Byers, S. Wray et al., “Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis,” Journal of Biological Chemistry, vol. 282, no. 32, pp. 23645–23654, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. C. H. Reynolds, J. C. Betts, W. P. Blackstock, A. R. Nebreda, and B. H. Anderton, “Phosphorylation sites on tau identified by nanoelectrospray mass spectrometry: differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun N-terminal kinase and P38, and glycogen synthase kinase-3beta,” Journal of Neurochemistry, vol. 74, no. 4, pp. 1587–1595, 2000. View at Publisher · View at Google Scholar · View at Scopus
  62. M. A. Utton, A. Vandecandelaere, U. Wagner et al., “Phosphorylation of tau by glycogen synthase kinase 3beta affects the ability of tau to promote microtubule self-assembly,” Biochemical Journal, vol. 323, no. 3, pp. 741–747, 1997. View at Google Scholar · View at Scopus
  63. G. Li, H. Yin, and J. Kuret, “Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules,” Journal of Biological Chemistry, vol. 279, no. 16, pp. 15938–15945, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. G. A. Morfini, G. Szebenyi, R. G. Elluru, N. Ratner, and S. T. Brady, “Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility,” The EMBO Journal, vol. 21, no. 3, pp. 281–293, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. P. J. Kennelly and E. G. Krebs, “Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases,” Journal of Biological Chemistry, vol. 266, no. 24, pp. 15555–15558, 1991. View at Google Scholar · View at Scopus
  66. A. R. Cole, F. Causeret, G. Yadirgi et al., “Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo,” Journal of Biological Chemistry, vol. 281, no. 24, pp. 16591–16598, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. A. Leroy, I. Landrieu, I. Huvent et al., “Spectroscopic studies of GSK3{beta} phosphorylation of the neuronal tau protein and its interaction with the N-terminal domain of apolipoprotein E,” Journal of Biological Chemistry, vol. 285, no. 43, pp. 33435–33444, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. F. Zhang, C. J. Phiel, L. Spece, N. Gurvich, and P. S. Klein, “Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to lithium. Evidence for autoregulation of GSK-3,” Journal of Biological Chemistry, vol. 278, no. 35, pp. 33067–33077, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. P. Polakis, “Casein kinase 1: a Wnt'er of disconnect,” Current Biology, vol. 12, no. 14, pp. R499–R501, 2002. View at Publisher · View at Google Scholar · View at Scopus
  70. T. J. Singh, N. Haque, I. Grundke-Iqbal, and K. Iqbal, “Rapid Alzheimer-like phosphorylation of tau by the synergistic actions of non-proline-dependent protein kinases and GSK- 3,” FEBS Letters, vol. 358, no. 3, pp. 267–272, 1995. View at Google Scholar
  71. J. H. Cho and G. V. Johnson, “Glycogen synthase kinase 3beta phosphorylates tau at both primed and unprimed sites. Differential impact on microtubule binding,” Journal of Biological Chemistry, vol. 278, no. 1, pp. 187–193, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. T. Li, C. A. Hawkes, H. Y. Qureshi, S. Kar, and H. K. Paudel, “Cyclin-dependent protein kinase 5 primes microtubule-associated protein tau site-specifically for glycogen synthase kinase 3beta,” Biochemistry, vol. 45, no. 10, pp. 3134–3145, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. J. Z. Wang, Q. Wu, A. Smith, I. Grundke-Iqbal, and K. Iqbal, “Tau is phosphorylated by GSK-3 at several sites found in Alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by A-kinase,” FEBS Letters, vol. 436, no. 1, pp. 28–34, 1998. View at Publisher · View at Google Scholar · View at Scopus
  74. M. P. M. Soutar, W. Y. Kim, R. Williamson et al., “Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain,” Journal of Neurochemistry, vol. 115, no. 4, pp. 974–983, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  75. F. Mukai, K. Ishiguro, Y. Sano, and S. C. Fujita, “Aternative splicing isoform of tau protein kinase I/glycogen synthase kinase 3beta,” Journal of Neurochemistry, vol. 81, no. 5, pp. 1073–1083, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. K. Saeki, M. Machida, Y. Kinoshita, R. Takasawa, and S. Tanuma, “Glycogen synthase kinase-3beta2 has lower phosphorylation activity to tau than glycogen synthase kinase-3beta1,” Biological and Pharmaceutical Bulletin, vol. 34, no. 1, pp. 146–149, 2011. View at Google Scholar
  77. Z. Castaño, P. R. Gordon-Weeks, and R. M. Kypta, “The neuron-specific isoform of glycogen synthase kinase-3beta is required for axon growth,” Journal of Neurochemistry, vol. 113, no. 1, pp. 117–130, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. S. G. Greenberg and P. Davies, “A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 15, pp. 5827–5831, 1990. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Hasegawa, M. Morishima-Kawashima, K. Takio, M. Suzuki, K. Titani, and Y. Ihara, “Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain,” Journal of Biological Chemistry, vol. 267, no. 24, pp. 17047–17054, 1992. View at Google Scholar · View at Scopus
  80. M. Morishima-Kawashima, M. Hasegawa, K. Takio et al., “Proline-directed and non-proline-directed phosphorylation of PHF-tau,” Journal of Biological Chemistry, vol. 270, no. 2, pp. 823–829, 1995. View at Publisher · View at Google Scholar · View at Scopus
  81. D. P. Hanger, J. C. Betts, T. L. Loviny, W. P. Blackstock, and B. H. Anderton, “New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry,” Journal of Neurochemistry, vol. 71, no. 6, pp. 2465–2476, 1998. View at Google Scholar · View at Scopus
  82. M. Morishima-Kawashima, M. Hasegawa, K. Takio et al., “Hyperphosphorylation of tau in PHF,” Neurobiology of Aging, vol. 16, no. 3, pp. 365–371, 1995. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Wray, M. Saxton, B. H. Anderton, and D. P. Hanger, “Direct analysis of tau from PSP brain identifies new phosphorylation sites and a major fragment of N-terminally cleaved tau containing four microtubule-binding repeats,” Journal of Neurochemistry, vol. 105, no. 6, pp. 2343–2352, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  84. J. J. Pei, E. Braak, H. Braak et al., “Distribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes,” Journal of Neuropathology and Experimental Neurology, vol. 58, no. 9, pp. 1010–1019, 1999. View at Google Scholar · View at Scopus
  85. I. Ferrer, M. D. Barrachina, and B. Puig, “Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer's diasese, Pick's disease, progressive supranuclear palsy and corticobasal degeneration,” Acta Neuropathologica, vol. 104, no. 6, pp. 583–591, 2002. View at Google Scholar · View at Scopus
  86. S. D. Harr, R. D. Hollister, and B. T. Hyman, “Glycogen synthase kinase 3 alpha and 3 beta do not colocalize with neurofibrillary tangles,” Neurobiology of Aging, vol. 17, no. 3, pp. 343–348, 1996. View at Publisher · View at Google Scholar · View at Scopus
  87. U. Wagner, M. A. Utton, J. M. Gallo, and C. C. Miller, “Cellular phosphorylation of tau by GSK-3beta influences tau binding to microtubules and microtubule organisation,” Journal of Cell Science, vol. 109, no. 6, pp. 1537–1543, 1996. View at Google Scholar · View at Scopus
  88. H. Sang, Z. Lu, Y. Li, B. G. Ru, W. Wang, and J. Chen, “Phosphorylation of tau by glycogen synthase kinase 3beta in intact mammalian cells influences the stability of microtubules,” Neuroscience Letters, vol. 312, no. 3, pp. 141–144, 2001. View at Publisher · View at Google Scholar · View at Scopus
  89. U. Wagner, J. Brownlees, N. G. Irving, F. R. Lucas, P. C. Salinas, and C. C. Miller, “Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated phosphorylation of tau in transfected mammalian cells,” FEBS Letters, vol. 411, no. 2-3, pp. 369–372, 1997. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Hong, D. C. Chen, P. S. Klein, and V. M. Lee, “Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3,” Journal of Biological Chemistry, vol. 272, no. 40, pp. 25326–25332, 1997. View at Publisher · View at Google Scholar · View at Scopus
  91. C. J. Phiel and P. S. Klein, “Molecular targets of lithium action,” Annual Review of Pharmacology and Toxicology, vol. 41, pp. 789–813, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. D. A. Cross, A. A. Culbert, K. A. Chalmers, L. Facci, S. D. Skaper, and A. D. Reith, “Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death,” Journal of Neurochemistry, vol. 77, no. 1, pp. 94–102, 2001. View at Publisher · View at Google Scholar · View at Scopus
  93. Q. H. Ye, G. Xu, D. Lv, Z. Cheng, J. S. Li, and Y. Hu, “Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3beta (GSK-3beta) inhibitors,” Bioorganic and Medicinal Chemistry, vol. 17, no. 13, pp. 4302–4312, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. M. Takahashi, K. Yasutake, and K. Tomizawa, “Lithium inhibits neurite growth and tau protein kinase I/glycogen synthase kinase-3beta-dependent phosphorylation of juvenile tau in cultured hippocampal neurons,” Journal of Neurochemistry, vol. 73, no. 5, pp. 2073–2083, 1999. View at Google Scholar · View at Scopus
  95. N. E. LaPointe, G. A. Morfini, G. Pigino et al., “The amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity,” Journal of Neuroscience Research, vol. 87, no. 2, pp. 440–451, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. G. R. Jackson, M. Wiedau-Pazos, T. K. Sang et al., “Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila,” Neuron, vol. 34, no. 4, pp. 509–519, 2002. View at Publisher · View at Google Scholar · View at Scopus
  97. I. Nishimura, Y. Yang, and B. Lu, “PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila,” Cell, vol. 116, no. 5, pp. 671–682, 2004. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Chatterjee, T. K. Sang, G. M. Lawless, and G. R. Jackson, “Dissociation of tau toxicity and phosphorylation: role of GSK-3beta, MARK and Cdk5 in a Drosophila model,” Human Molecular Genetics, vol. 18, no. 1, pp. 164–177, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  99. J. M. Shulman and M. B. Feany, “Genetic modifiers of tauopathy in Drosophila,” Genetics, vol. 165, no. 3, pp. 1233–1242, 2003. View at Google Scholar · View at Scopus
  100. X. Chen, Y. Li, J. Huang et al., “Study of tauopathies by comparing Drosophila and human tau in Drosophila,” Cell and Tissue Research, vol. 329, no. 1, pp. 169–178, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  101. G. Drewes, A. Ebneth, U. Preuss, E. M. Mandelkow, and E. Mandelkow, “MARK, a novel family of protein kinases that phosphorylate microtubule- associated proteins and trigger microtubule disruption,” Cell, vol. 89, no. 2, pp. 297–308, 1997. View at Google Scholar · View at Scopus
  102. E. M. Mandelkow, E. Thies, B. Trinczek, J. Biernat, and E. Mandelkow, “MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons,” Journal of Cell Biology, vol. 167, no. 1, pp. 99–110, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  103. T. Timm, K. Balusamy, X. Li, J. Biernat, E. Mandelkow, and E. M. Mandelkow, “Glycogen Synthase Kinase (GSK) 3beta directly phosphorylates serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2,” Journal of Biological Chemistry, vol. 283, no. 27, pp. 18873–18882, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  104. G. Heidary and M. E. Fortini, “Identification and characterization of the Drosophila tau homolog,” Mechanisms of Development, vol. 108, no. 1-2, pp. 171–178, 2001. View at Publisher · View at Google Scholar · View at Scopus
  105. W. Noble, D. P. Hanger, and J. M. Gallo, “Transgenic mouse models of tauopathy in drug discovery,” CNS and Neurological Disorders—Drug Targets, vol. 9, no. 4, pp. 403–428, 2010. View at Google Scholar · View at Scopus
  106. J. J. Lucas, F. Hernandez, P. Gomez-Ramos, M. A. Moran, R. Hen, and J. Avila, “Decreased nuclear ss-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3ss conditional transgenic mice,” The EMBO Journal, vol. 20, no. 1-2, pp. 27–39, 2001. View at Google Scholar
  107. F. Hernández, J. I. Borrell, C. Guaza, J. Avila, and J. J. Lucas, “Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments,” Journal of Neurochemistry, vol. 83, no. 6, pp. 1529–1533, 2002. View at Publisher · View at Google Scholar · View at Scopus
  108. T. Engel, F. Hernández, J. Avila, and J. J. Lucas, “Full reversal of Alzheimer's disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3,” Journal of Neuroscience, vol. 26, no. 19, pp. 5083–5090, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. K. Spittaels, C. Van den Haute, J. Van Dorpe et al., “Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice,” Journal of Biological Chemistry, vol. 275, no. 52, pp. 41340–41349, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  110. M. Perez, A. I. Rojo, F. Wandosell, J. Diaz-Nido, and J. Avila, “Prion peptide induces neuronal cell death through a pathway involving glycogen synthase kinase 3,” Biochemical Journal, vol. 372, no. 1, pp. 129–136, 2003. View at Google Scholar
  111. W. Noble, E. Planel, C. Zehr et al., “Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 19, pp. 6990–6995, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. H. Nakashima, T. Ishihara, P. Suguimoto et al., “Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies,” Acta Neuropathologica, vol. 110, no. 6, pp. 547–556, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  113. L. Sereno, M. Coma, M. Rodriguez et al., “A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo,” Neurobiology of Disease, vol. 35, no. 3, pp. 359–367, 2009. View at Google Scholar
  114. K. Leroy, K. Ando, C. Héraud et al., “Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology,” Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 705–719, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus