PP2A and Alzheimer disease

Current Alzheimer Research

Volumn 9, Issue 2, 2012, Pages 248-256

  Torrent, L ^a   Ferrer, I ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Alzheimer disease; Methylation; Phosphorylation; Protein phosphatase 2 A

Indexed keywords

AMYLOID BETA PROTEIN; CYCLIN DEPENDENT KINASE 5; PHOSPHOPROTEIN PHOSPHATASE 2A; PROTEIN KINASE B; TAU PROTEIN; THIAMINE PYROPHOSPHOKINASE;

ALZHEIMER DISEASE; AMNESIA; ARTICLE; CATALYSIS; CELL CULTURE; CELL CYCLE REGULATION; CELL STRUCTURE; CRYSTAL STRUCTURE; CYTOSKELETON; CYTOSOL; DEPHOSPHORYLATION; DISEASE COURSE; DOWN REGULATION; ENTORHINAL CORTEX; ENZYME ACTIVITY; GENE EXPRESSION; HIPPOCAMPUS; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; IN VITRO STUDY; LEARNING DISORDER; MITOCHONDRION; NONEQUIVALENT CONTROL GROUP; NONHUMAN; NUCLEUS ACCUMBENS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; RNA ANALYSIS; SIGNAL TRANSDUCTION; UPREGULATION;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; BRAIN; FEMALE; HUMANS; INDIVIDUALITY; MALE; MIDDLE AGED; POSTMORTEM CHANGES; PROTEIN PHOSPHATASE 2;

EID: 84857727442     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/156720512799361682     Document Type: Article

References (97)

1. Andreadis A. Misregulation of tau alternative splicing in neurodegeneration and dementia. Prog Mol Subcell Biol 44:89-107 (2006).
2. Goedert M. Tau protein and the neurofibrillary pathology of Alzheimer's disease. Trends Neurosci 16: 460-5 (1993).
3. Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci 8: 663-72 (2007).
4. Csortos C, Zolnierowicz S, Bakó E, Durbin SD, DePaoli-Roach AA. High complexity in the expression of the B' subunit of protein phosphatase 2A0. Evidence for the existence of at least seven novel isoforms. J Biol Chem 271:2578-88 (1996).
5. Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci USA 72: 1858-62 (1975).
6. Bramblett GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VM. Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron, 1993. 10(6): p. 1089-99.
7. Hirokawa N. Neuronal cytoskeleton: molecular architecture, function and dynamics. Tanpakushitsu Kakusan Koso. 35(4 Suppl): 480-507 (1990).
8. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 13: 83-117 (1997).
9. Trojanowski JQ, Lee VM. Phosphorylation of paired helical filament tau in Alzheimer's disease neurofibrillary lesions: focusing on phosphatases. FASEB J 9: 1570-6 (1995).
10. Ferrer I, Gomez-Isla T, Puig B, Freixes M, Ribé E, Dalfó E, et al. Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer's disease and tauopathies. Curr Alzheimer Res 2: 3-18 (2005)
11. Gong CX, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K. Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. J Biol Chem 275: 5535-44 (2000).
12. Wang JZ, Gong CX, Zaidi T, Grundke-Iqbal I, Iqbal K. Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. J Biol Chem 270: 4854-60 (1995).
13. Sontag E, Nunbhakdi-Craig V, Sontag JM, Diaz-Arrastia R, Ogris E, et al. Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J Neurosci 27: 2751-9 (2007).
14. Saito T, Ishiguro K, Uchida T, Miyamoto E, Kishimoto T, Hisanaga S. In situ dephosphorylation of tau by protein phosphatase 2A and 2B in fetal rat primary cultured neurons. FEBS Lett 376: 238-42 (1995).
15. Wang JZ, Grundke-Iqbal I, Iqbal K. Restoration of biological activity of Alzheimer abnormally phosphorylated tau by dephosphorylation with protein phosphatase-2A, -2B and -1. Brain Res Mol Brain Res 38: 200-8 (1996).
16. Goedert M, Cohen ES, Jakes R, Cohen P. p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease. FEBS Lett 312: 95-9 (1992).
17. Tamura S, Kikuchi H, Kikuchi K, Hiraga A, Tsuiki S. Purification and subunit structure of a high-molecular-weight phosphoprotein phosphatase (phosphatase II) from rat liver. Eur J Biochem 104: 347-55 (1980).
18. Usui H, Imazu M, Maeta K, Tsukamoto H, Azuma K, Takeda M. Three distinct forms of type 2A protein phosphatase in human erythrocyte cytosol. J Biol Chem 263: 3752-61 (1988).
19. Cohen PT. Novel protein serine/threonine phosphatases: variety is the spice of life. Trends Biochem Sci 22: 245-51 (1997).
20. Cohen PT, Brewis ND, Hughes V, Mann DJ. Protein serine/threonine phosphatases; an expanding family. FEBS Lett 268: 355-9 (1990).
21. Mayer-Jaekel RE, Hemmings BA. Protein phosphatase 2A - a 'menage a trois'. Trends Cell Biol 4: 287-91 (1994).
22. Stone SR, Hofsteenge J, Hemmings BA. Molecular cloning of cDNAs encoding two isoforms of the catalytic subunit of protein phosphatase 2A. Biochemistry 26: 7215-20 (1987).
23. Arino J, Woon CW, Brautigan DL, Miller TB Jr, Johnson GL. Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes. Proc Natl Acad Sci U S A 85: 4252-6 (1988).
24. Khew-Goodall Y, Mayer RE, Maurer F, Stone SR, Hemmings BA. Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes. Biochemistry 30: 89-97 (1991).
25. Khew-Goodall Y, Hemmings BA. Tissue-specific expression of mRNAs encoding alpha- and beta-catalytic subunits of protein phosphatase 2A. FEBS Lett 238: 265-8 (1988).
26. Ruediger R, Roeckel D, Fait J, Bergqvist A, Magnusson G, Walter G. Identification of binding sites on the regulatory A subunit of protein phosphatase 2A for the catalytic C subunit and for tumor antigens of simian virus 40 and polyomavirus. Mol Cell Biol 12: 4872-82 (1992).
27. Ruediger R, Hentz M, Fait J, Mumby M, Walter G. Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens. J Virol 68: 123-9 (1994).
28. Hemmings BA, Adams-Pearson C, Maurer F, Müller P, Goris J, Merlevede W, et al. Alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure. Biochemistry 29: 3166-73 (1990).
29. Andrade MA, Bork P. HEAT repeats in the Huntington's disease protein. Nat Genet 11: 115-6 (1995).
30. Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D. The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. Cell 96: 99-110 (1999).
31. Mayer RE, Hendrix P, Cron P, Matthies R, Stone SR, Goris J, et al. Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence for a neuronal-specific isoform. Biochemistry 30: 3589-97 (1991).
32. Strack S, Chang D, Zaucha JA, Colbran RJ, Wadzinski BE. Cloning and characterization of B delta, a novel regulatory subunit of protein phosphatase 2A. FEBS Lett 460: 462-6 (1999).
33. Strack S, Zaucha JA, Ebner FF, Colbran RJ, Wadzinski BE. Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits. J Comp Neurol 392: 515-27 (1998).
34. van Lookeren Campagne M, Okamoto K, Prives C, Gill R. Developmental expression and co-localization of cyclin G1 and the B' subunits of protein phosphatase 2a in neurons. Brain Res Mol Brain Res 64: 1-10 (1999).
35. Schmidt K, Kins S, Schild A, Nitsch RM, Hemmings BA, Götz J. Diversity, developmental regulation and distribution of murine PR55/B subunits of protein phosphatase 2A. Eur J Neurosci 16: 2039-48 (2002).
36. Sontag E, Nunbhakdi-Craig V, Lee G, Brandt R, Kamibayashi C, Kuret J, White, et al. Molecular interactions among protein phosphatase 2A, tau, and microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies. J Biol Chem 274: 25490-8 (1999).
37. Sontag E, Nunbhakdi-Craig V, Lee G, Bloom GS, Mumby MC. Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron 17: 1201-7 (1996).
38. Götz J, Probst A, Ehler E, Hemmings B, Kues W. Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic subunit Calpha. Proc Natl Acad Sci U S A 95: 12370-5 (1995).
39. Janssens V, Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 353: 417-39 (2001).
40. Li M, Makkinje A, Damuni Z. Molecular identification of I1PP2A, a novel potent heat-stable inhibitor protein of protein phosphatase 2A. Biochemistry 35: 6998-7002 (1996).
41. Honkanen RE, Codispoti BA, Tse K, Boynton AL, Honkanan RE. Characterization of natural toxins with inhibitory activity against serine/threonine protein phosphatases. Toxicon 32: 339-50 (1994).
42. Li M, Guo H, Damuni Z. Purification and characterization of two potent heat-stable protein inhibitors of protein phosphatase 2A from bovine kidney. Biochemistry 34: 1988-96 (1995).
43. Li M, Makkinje A, Damuni Z. The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A. J Biol Chem 271: 11059-62 (1996).
44. Sontag E. Protein phosphatase 2A: the Trojan Horse of cellular signaling. Cell Signal 13: 7-16 (2001).
45. Goedert M, Satumtira S, Jakes R, Smith MJ, Kamibayashi C, White CL et al. Reduced binding of protein phosphatase 2A to tau protein with frontotemporal dementia and parkinsonism linked to chromosome 17 mutations. J Neurochem 75: 2155-62 (2000).
46. Kins S, Crameri A, Evans DR, Hemmings BA, Nitsch RM, Gotz J. Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. J Biol Chem 276: 38193-200 (2001).
47. Bennecib M, Gong CX, Grundke-Iqbal I, Iqbal K. Role of protein phosphatase-2A and -1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain. FEBS Lett 485: 87-93 (2000).
48. Gong CX, Wegiel J, Lidsky T, Zuck L, Avila J, Wisniewski HM, et al. Regulation of phosphorylation of neuronal microtubuleassociated proteins MAP1b and MAP2 by protein phosphatase-2A and -2B in rat brain. Brain Res 853: 299-309 (2000).
49. Lee J, Hong H, Im J, Byun H, Kim D. The formation of PHF-1 and SMI-31 positive dystrophic neurites in rat hippocampus following acute injection of okadaic acid. Neurosci Lett 282: 49-52 (2000).
50. Sun L, Liu SY, Zhou XW, Wang XC, Liu R, Wang Q, Wang JZ. Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats. Neuroscience 118: 1175-82 (2003).
51. Planel E, Yasutake K, Fujita SC, Ishiguro K. Inhibition of protein phosphatase 2A overrides tau protein kinase I/glycogen synthase kinase 3 beta and cyclin-dependent kinase 5 inhibition and results in tau hyperphosphorylation in the hippocampus of starved mouse. J Biol Chem 276: 34298-306 (2001).
52. Zhou XW, Winblad B, Guan Z, Pei JJ. Interactions Between Glycogen Synthase Kinase 3beta, Protein Kinase B, and Protein Phosphatase 2A in Tau Phosphorylation in Mouse N2a Neuroblastoma Cells. J Alzheimers Dis, 2009.
53. Kim D, Su J, Cotman CW. Sequence of neurodegeneration and accumulation of phosphorylated tau in cultured neurons after okadaic acid treatment. Brain Res 839: 253-62 (1999).
54. Tanaka T, Zhong J, Iqbal K, Trenkner E, Grundke-Iqbal I. The regulation of phosphorylation of tau in SY5Y neuroblastoma cells: the role of protein phosphatases. FEBS Lett 426: 248-54 (1998).
55. Gong CX, Shaikh S, Wang JZ, Zaidi T, Grundke-Iqbal I, Iqbal K. Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain. J Neurochem 65: 732-8 (1995).
56. Vogelsberg-Ragaglia V, et al. PP2A mRNA expression is quantitatively decreased in Alzheimer's disease hippocampus. Exp Neurol 168: 402-12 (2001).
57. Loring JF, Wen X, Lee JM, Seilhamer J, Somogyi R. A gene expression profile of Alzheimer's disease. DNA Cell Biol 20: 683-95 (2001).
58. Zhao WQ, Feng C, Alkon DL. Impairment of phosphatase 2A contributes to the prolonged MAP kinase phosphorylation in Alzheimer's disease fibroblasts. Neurobiol Dis 14: 458-69 (2003).
59. Nicolia V, Fuso A, Cavallaro RA, Di Luzio A, Scarpa S. B vitamin deficiency promotes tau phosphorylation through regulation of GSK3beta and PP2A. J Alzheimers Dis 19: 895-907 (2010)
60. Sontag E, Luangpirom A, Hladik C, Mudrak I, Ogris E, Speciale S, White CL 3rd. Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology. J Neuropathol Exp Neurol 63: 287-301 (2004).
61. Liang Z, Liu F, Iqbal K, Grundke-Iqbal I, Wegiel J, Gong CX. Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome. J Alzheimers Dis 13: 295-302 (2008).
62. Baharians Z, Schönthal AH. Autoregulation of protein phosphatase type 2A expression. J Biol Chem 273: 19019-24 (1998)
63. Xie H, Clarke S. Protein phosphatase 2A is reversibly modified by methyl esterification at its C-terminal leucine residue in bovine brain. J Biol Chem 269: 1981-4 (1994).
64. Bryant JC, Westphal RS, Wadzinski BE. Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit. Biochem J 339: 241-6 (1999).
65. Wu J, Tolstykh T, Lee J, Boyd K, Stock JB, Broach JR. Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J 19: 5672-81 (2000).
66. Lee J, Stock J. Protein phosphatase 2A catalytic subunit is methylesterified at its carboxyl terminus by a novel methyltransferase. J Biol Chem 268: 19192-5 (1993).
67. De Baere I, Derua R, Janssens V, Van Hoof C, Waelkens E, Merlevede W, Goris J. Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue. Biochemistry 38: 16539-47 (1999).
68. George RR, Harris R, Nunn CM, Cramer R, Djordjevic S. Chaperonin assisted overexpression, purification, and characterisation of human PP2A methyltransferase. Protein Expr Purif 26: 266-74 (2002).
69. Lee J, et al. A specific protein carboxyl methylesterase that demethylates phosphoprotein phosphatase 2A in bovine brain. Proc Natl Acad Sci U S A 93: 6043-7 (1996).
70. Ogris E, Du X, Nelson KC, Mak EK, Yu XX, Lane WS, Pallas DC. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. J Biol Chem 274:14382-91 (1999).
71. Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y. Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell 133: 154-63 (2008).
72. Longin S, Jordens J, Martens E, Stevens I, Janssens V, Rondelez E, De Baere I, Derua R, Waelkens E, Goris J, Van Hoof C. An inactive protein phosphatase 2A population is associated with methylesterase and can be re-activated by the phosphotyrosyl phosphatase activator. Biochem J 380: 111-9 (2004).
73. Sunahori K, Juang YT, Tsokos GC. Methylation status of CpG islands flanking a cAMP response element motif on the protein phosphatase 2Ac alpha promoter determines CREB binding and activity. J Immunol 182: 1500-8 (2009)
74. Chen J, Martin BL, Brautigan DL. Regulation of protein serinethreonine phosphatase type-2A by tyrosine phosphorylation. Science 257: 1261-4 (1992).
75. Chen J, Parsons S, Brautigan DL. Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts. J Biol Chem 269: 7957-62 (1994).
76. Brautigan DL. Flicking the switches: phosphorylation of serine/threonine protein phosphatases. Semin Cancer Biol 6: 211-7 (1995).
77. Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL 3rd. Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol 63: 1080-91 (2004).
78. Zhou XW, Gustafsson JA, Tanila H, Bjorkdahl C, Liu R, Winblad B, Pei JJ. Tau hyperphosphorylation correlates with reduced methylation of protein phosphatase 2A. Neurobiol Dis 31: 386-94 (2008).
79. Tanimukai H, Grundke-Iqbal I, Iqbal K. Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer's disease. Am J Pathol 166: 1761-71 (2005).
80. Chen S, Li B, Grundke-Iqbal I, Iqbal K. I1PP2A affects tau phosphorylation via association with the catalytic subunit of protein phosphatase 2A. J Biol Chem 283: 10513-21 (2008).
81. Liu R, Zhou XW, Tanila H, Bjorkdahl C, Wang JZ, Guan ZZ, Cao Y, Gustafsson JA, Winblad B, Pei JJ. Phosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology. J Cell Mol Med 12: 241-57 (2008).
82. Xu Y, et al. Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation. Mol Cell 31: 873-85 (2008).
83. Xing Y, Xu Y, Chen Y, Jeffrey PD, Chao Y, Lin Z, Li Z, Strack S, Stock JB, Shi Y. Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins. Cell 127: 341-53 (2006).
84. Cho US, Xu W. Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature 445: 53-7 (2007).
85. Ruediger R, Pham HT, Walter G. Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene. Oncogene 20: 1892-9 (2001).
86. Ruediger R, Pham HT, Walter G. Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the A alpha subunit gene. Oncogene 20: 10-5 (2001).
87. Gong CX, Singh TJ, Grundke-Iqbal I, Iqbal K. Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem 61: 921-7 (1993).
88. Gong C.X, Grundke-Iqbal I, Iqbal K. Dephosphorylation of Alzheimer's disease abnormally phosphorylated tau by protein phosphatase-2A. Neuroscience 61: 765-72 (1994).
89. Liu F, et al. Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur J Neurosci 22: 1942-50 (2005).
90. Virshup DM. Protein phosphatase 2A: a panoply of enzymes. Curr Opin Cell Biol 12: 180-5 (2000).
91. Lechward K, et al. Protein phosphatase 2A: variety of forms and diversity of functions. Acta Biochim Pol 48: 921-33 (2001).
92. Tian Q, Wang J. Role of serine/threonine phospjhatase in Alzheimer's disease. Neurosignals 1: 262-9 (2002).
93. Gong CX, Iqbal K. Hyper-phosphorylation of microtubuleassociated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem 15: 2321-8 (2008).
94. Deters N, Ittner LM, Gtz J. Substrate-specific reduction of PP2A activity exaggerates tau pathology. Biochem Biophys Res Commun 379: 400-5 (2009).
95. Iqbal K, Liu F, Gong CX, Alonso A del C, Grundke-Iqbal I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118: 53-69 (2009).
96. Chohan MO, Khatoon S, Iqbal IG, Iqbal K. Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by memantine. FEBS Lett 580: 3973-9 (2006).
97. Tsujio I, Zaidi T, Kotula L, Grundke-Iqbal I, Iqbal K. Inhibitors of protein phosphatase-2A from human brain structures, immunocytological localization and activituies towards dephosphorylation of the Alzheimer type hyperphosphorylated tau. FEBS Lett 579: 363-72 (2005).