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Gene Review

Mapt  -  microtubule-associated protein tau

Mus musculus

Synonyms: AI413597, AW045860, Microtubule-associated protein tau, Mtapt, Neurofibrillary tangle protein, ...
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Disease relevance of Mapt


Psychiatry related information on Mapt


High impact information on Mapt


Chemical compound and disease context of Mapt


Biological context of Mapt

  • Stable transfection of a kinase-deficient ILK mutant (DN-ILK) resulted in aberrant tau phosphorylation in N1E-115 cells at sites recognized by the Tau-1 antibody that are identical to some of the phosphorylation sites in paired helical filaments, PHF-tau, in brains of patients with Alzheimer's disease [16].
  • The same pathological alterations are known from AD patients or transgenic models overexpressing Tau or ApoE, however, these disturbances in axonal transport occur in the absence of any signs of concomitant Tau pathology [17].
  • To investigate how Tau alterations provoke neurodegeneration we generated transgenic mice expressing human Tau with four tubulin-binding repeats (increased by FTDP-17 splice donor mutations) and three FTDP-17 missense mutations: G272V, P301L, and R406W [3].
  • 4. These results imply a specific developmental regulation of mRNA translation of Tau, and indicate that, after the period of synapse formation is complete, and therefore axonal growth has finished (P20), only a limited number of new Tau molecules are synthesized [18].
  • The mechanism of neuron death was investigated in htau mice, and surprisingly, the presence of tau filaments did not correlate directly with death within individual cells, suggesting that cell death can occur independently of NFT formation [19].

Anatomical context of Mapt


Associations of Mapt with chemical compounds

  • Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert [23].
  • Using the high-resolution two-dimensional polyacrylamide gel electrophoresis system, we have resolved more than 60 distinct Tau isoforms in the adult mouse brain [24].
  • The present data show that estradiol, in vivo, induces a transient activation of GSK3 in the adult female rat hippocampus, followed by a more sustained inhibition, as inferred from phosphorylation levels of Tau [25].
  • Dyrk1A is found in sarkosyl-insoluble fractions which are enriched in phosphorylated tau in AD brains, thus suggesting a possible association of Dyrk1A with neurofibrillary tangle pathology [26].
  • S3C-8 cells, overexpressing sema3C, were significantly more neuritogenic for CGN than poly l-lysine (PLL), a positive substrate for CGNs, as assessed by the measurement of the length of neurites and confirmed by Tau expression along the time of culture [27].
  • On the other hand, the investigation of Tau protein at Ser-262 showed that interference in the insulin/PI3K and mTor signaling potentially influenced the Tau phosphorylation status at sites where only one of two enzymes (in this case PP2A) is involved in the regulation [28].

Physical interactions of Mapt

  • This effect is likely to be caused by interference with the Fyn-Tau-microtubuli cascade rather than inactivation of the kinase, because Fyn bound to the mutant Tau retains activity [22].
  • It has been suggested that the deleterious effects of the allele E4 of apolipoprotein E (apoE) in Alzheimer's disease (AD) are related to its inability to interact with the microtubule associated protein tau and to thereby prevent its hyperphosphorylation [29].

Regulatory relationships of Mapt


Other interactions of Mapt

  • ILK inactivation resulted in an increase in the active form but a decrease in the inactive form of GSK-3beta, which is a candidate kinase involved in PHF-tau formation [16].
  • Disease-related modifications in tau affect the interaction between Fyn and Tau [31].
  • Hippocampal samples taken from FAD mutant (I213T) PS1 knock-in mice contained hyperphosphorylated tau that reacted with various phosphodependent tau antibodies and with Alz50, which recognizes the conformational change of PHF tau [32].
  • BDNF stimulation of neuronally differentiated P19 mouse embryonic carcinoma cells resulted in a rapid decrease in tau phosphorylation, at phosphorylation sites recognized by Tau 1, AT 8, AT 180 and p 262-Tau antibodies [20].
  • APPsw transgenic mice bearing the "Swedish" amyloid precursor protein (APP) mutation and JNPL3 transgenic mice bearing the P301L (Tau) mutation were compared to control non-transgenic (NT) mice in an extensive behavioral test battery administered between 5 and 8.5 months of age [21].

Analytical, diagnostic and therapeutic context of Mapt

  • Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression of microtubular components showed that levels of Mbeta4-tubulin and Tau mRNAs were higher in the murine sensitive neoplasms than in the refractory ones [33].
  • Seven days after MDM injection, mice were killed and CNS tissue was collected and subjected to immunocytochemical and Western blot assays for leukocyte and neural antigens, GSK-3beta, and key kinase substrates such as beta-catenin and Tau [34].
  • The 56,000-dalton Tau antigen appeared to share only two methionine-tryptic peptides with the large species of SV40 tumor antigen, as determined by ion-exchange and paper chromatographies [35].
  • U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy [36].
  • Hyperphosphorylation of Tau and filopodial retraction following microinjection of protein kinase C catalytic subunits [37].


  1. Transgenic mouse models for Alzheimer's disease: the role of GSK-3B in combined amyloid and tau-pathology. Muyllaert, D., Terwel, D., Borghgraef, P., Devijver, H., Dewachter, I., Van Leuven, F. Rev. Neurol. (Paris) (2006) [Pubmed]
  2. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Paul Murphy, M., Baker, M., Yu, X., Duff, K., Hardy, J., Corral, A., Lin, W.L., Yen, S.H., Dickson, D.W., Davies, P., Hutton, M. Nat. Genet. (2000) [Pubmed]
  3. FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and Tau filaments in forebrain. Lim, F., Hernández, F., Lucas, J.J., Gómez-Ramos, P., Morán, M.A., Avila, J. Mol. Cell. Neurosci. (2001) [Pubmed]
  4. Increased expression of beta-amyloid protein precursor and microtubule-associated protein tau during the differentiation of murine embryonal carcinoma cells. Fukuchi, K., Deeb, S.S., Kamino, K., Ogburn, C.E., Snow, A.D., Sekiguchi, R.T., Wight, T.N., Piussan, H., Martin, G.M. J. Neurochem. (1992) [Pubmed]
  5. Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease. Sze, C.I., Su, M., Pugazhenthi, S., Jambal, P., Hsu, L.J., Heath, J., Schultz, L., Chang, N.S. J. Biol. Chem. (2004) [Pubmed]
  6. Site-specific dephosphorylation of tau of apolipoprotein E-deficient and control mice by M1 muscarinic agonist treatment. Genis, I., Fisher, A., Michaelson, D.M. J. Neurochem. (1999) [Pubmed]
  7. Mutations causing neurodegenerative tauopathies. Goedert, M., Jakes, R. Biochim. Biophys. Acta (2005) [Pubmed]
  8. BAG-1 associates with Hsc70.Tau complex and regulates the proteasomal degradation of Tau protein. Elliott, E., Tsvetkov, P., Ginzburg, I. J. Biol. Chem. (2007) [Pubmed]
  9. Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Sontag, E., Nunbhakdi-Craig, V., Lee, G., Bloom, G.S., Mumby, M.C. Neuron (1996) [Pubmed]
  10. An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice. Le Corre, S., Klafki, H.W., Plesnila, N., Hübinger, G., Obermeier, A., Sahagún, H., Monse, B., Seneci, P., Lewis, J., Eriksen, J., Zehr, C., Yue, M., McGowan, E., Dickson, D.W., Hutton, M., Roder, H.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Role for neuronal insulin resistance in neurodegenerative diseases. Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., Schubert, D., Kondo, T., Alber, J., Galldiks, N., Küstermann, E., Arndt, S., Jacobs, A.H., Krone, W., Kahn, C.R., Brüning, J.C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Ohshima, T., Ward, J.M., Huh, C.G., Longenecker, G., Veeranna, n.u.l.l., Pant, H.C., Brady, R.O., Martin, L.J., Kulkarni, A.B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  13. Characterization of tau antigens isolated from uninfected and simian virus 40-infected monkey cells and papovavirus-transformed cells. Simmons, D.T. J. Virol. (1980) [Pubmed]
  14. Species differences in cerebral taurine concentrations correlate with brain water content. Puka, M., Sundell, K., Lazarewicz, J.W., Lehmann, A. Brain Res. (1991) [Pubmed]
  15. Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Duka, T., Rusnak, M., Drolet, R.E., Duka, V., Wersinger, C., Goudreau, J.L., Sidhu, A. FASEB J. (2006) [Pubmed]
  16. Inactivation of integrin-linked kinase induces aberrant tau phosphorylation via sustained activation of glycogen synthase kinase 3beta in N1E-115 neuroblastoma cells. Ishii, T., Furuoka, H., Muroi, Y., Nishimura, M. J. Biol. Chem. (2003) [Pubmed]
  17. Axonopathy in an APP/PS1 transgenic mouse model of Alzheimer's disease. Wirths, O., Weis, J., Szczygielski, J., Multhaup, G., Bayer, T.A. Acta Neuropathol. (2006) [Pubmed]
  18. The rate of Tau synthesis is differentially regulated during postnatal development in mouse cerebellum. Vilá-Ortiz, G.J., Santa-Coloma, T.A., Carminatti, H., Radrizzani, M. Cell. Mol. Neurobiol. (2001) [Pubmed]
  19. Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. Andorfer, C., Acker, C.M., Kress, Y., Hof, P.R., Duff, K., Davies, P. J. Neurosci. (2005) [Pubmed]
  20. Brain-derived neurotrophic factor induces a rapid dephosphorylation of tau protein through a PI-3 Kinase signalling mechanism. Elliott, E., Atlas, R., Lange, A., Ginzburg, I. Eur. J. Neurosci. (2005) [Pubmed]
  21. Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's disease: linkage of poorer cognitive performance to tau pathology in forebrain. Arendash, G.W., Lewis, J., Leighty, R.E., McGowan, E., Cracchiolo, J.R., Hutton, M., Garcia, M.F. Brain Res. (2004) [Pubmed]
  22. Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau. Klein, C., Kramer, E.M., Cardine, A.M., Schraven, B., Brandt, R., Trotter, J. J. Neurosci. (2002) [Pubmed]
  23. Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert. Engel, T., Goñi-Oliver, P., Lucas, J.J., Avila, J., Hernández, F. J. Neurochem. (2006) [Pubmed]
  24. Heterogeneity of Tau proteins during mouse brain development and differentiation of cultured neurons. Larcher, J.C., Boucher, D., Ginzburg, I., Gros, F., Denoulet, P. Dev. Biol. (1992) [Pubmed]
  25. Estradiol inhibits GSK3 and regulates interaction of estrogen receptors, GSK3, and beta-catenin in the hippocampus. Cardona-Gomez, P., Perez, M., Avila, J., Garcia-Segura, L.M., Wandosell, F. Mol. Cell. Neurosci. (2004) [Pubmed]
  26. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Ferrer, I., Barrachina, M., Puig, B., Martínez de Lagrán, M., Martí, E., Avila, J., Dierssen, M. Neurobiol. Dis. (2005) [Pubmed]
  27. Semaphorin 3C preserves survival and induces neuritogenesis of cerebellar granule neurons in culture. Moreno-Flores, M.T., Martín-Aparicio, E., Martín-Bermejo, M.J., Agudo, M., McMahon, S., Avila, J., Díaz-Nido, J., Wandosell, F. J. Neurochem. (2003) [Pubmed]
  28. Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau. Meske, V., Albert, F., Ohm, T.G. J. Biol. Chem. (2008) [Pubmed]
  29. Phosphorylation of tau in apolipoprotein E-deficient mice. Genis, I., Gordon, I., Sehayek, E., Michaelson, D.M. Neurosci. Lett. (1995) [Pubmed]
  30. Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models. Götz, J., Schild, A., Hoerndli, F., Pennanen, L. Int. J. Dev. Neurosci. (2004) [Pubmed]
  31. Disease-related modifications in tau affect the interaction between Fyn and Tau. Bhaskar, K., Yen, S.H., Lee, G. J. Biol. Chem. (2005) [Pubmed]
  32. Formation of tau inclusions in knock-in mice with familial Alzheimer disease (FAD) mutation of presenilin 1 (PS1). Tanemura, K., Chui, D.H., Fukuda, T., Murayama, M., Park, J.M., Akagi, T., Tatebayashi, Y., Miyasaka, T., Kimura, T., Hashikawa, T., Nakano, Y., Kudo, T., Takeda, M., Takashima, A. J. Biol. Chem. (2006) [Pubmed]
  33. Tau expression in model adenocarcinomas correlates with docetaxel sensitivity in tumour-bearing mice. Veitia, R., Bissery, M.C., Martinez, C., Fellous, A. Br. J. Cancer (1998) [Pubmed]
  34. Neuroprotective mechanisms of lithium in murine human immunodeficiency virus-1 encephalitis. Dou, H., Ellison, B., Bradley, J., Kasiyanov, A., Poluektova, L.Y., Xiong, H., Maggirwar, S., Dewhurst, S., Gelbard, H.A., Gendelman, H.E. J. Neurosci. (2005) [Pubmed]
  35. Identification and partial characterization of new antigens from simian virus 40-transformed mouse cells. Chang, C., Simmons, D.T., Martin, M.A., Mora, P.T. J. Virol. (1979) [Pubmed]
  36. U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy. Hatakeyama, S., Matsumoto, M., Kamura, T., Murayama, M., Chui, D.H., Planel, E., Takahashi, R., Nakayama, K.I., Takashima, A. J. Neurochem. (2004) [Pubmed]
  37. Hyperphosphorylation of Tau and filopodial retraction following microinjection of protein kinase C catalytic subunits. Cressman, C.M., Shea, T.B. J. Neurosci. Res. (1995) [Pubmed]
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