Abstract
Tau is a neuronal microtubule-associated protein that promotes microtubule assembly, stability, and bundling in axons. Two distinct regions of tau are important for the tau-microtubule interaction, a relatively well-characterized "repeat region" in the carboxyl terminus (containing either three or four imperfect 18-amino acid repeats separated by 13- or 14-amino acid long inter-repeats) and a more centrally located, relatively poorly characterized proline-rich region. By using amino-terminal truncation analyses of tau, we have localized the microtubule binding activity of the proline-rich region to Lys215-Asn246 and identified a small sequence within this region, 215KKVAVVR221, that exerts a strong influence on microtubule binding and assembly in both three- and four-repeat tau isoforms. Site-directed mutagenesis experiments indicate that these capabilities are derived largely from Lys215/Lys216 and Arg221. In marked contrast to synthetic peptides corresponding to the repeat region, peptides corresponding to Lys215-Asn246 and Lys215-Thr222 alone possess little or no ability to promote microtubule assembly, and the peptide Lys215-Thr222 does not effectively suppress in vitro microtubule dynamics. However, combining the proline-rich region sequences (Lys215-Asn246) with their adjacent repeat region sequences within a single peptide (Lys215-Lys272) enhances microtubule assembly by 10-fold, suggesting intramolecular interactions between the proline-rich and repeat regions. Structural complexity in this region of tau also is suggested by sequential amino-terminal deletions through the proline-rich and repeat regions, which reveal an unusual pattern of loss and gain of function. Thus, these data lead to a model in which efficient microtubule binding and assembly activities by tau require intramolecular interactions between its repeat and proline-rich regions. This model, invoking structural complexity for the microtubule-bound conformation of tau, is fundamentally different from previous models of tau structure and function, which viewed tau as a simple linear array of independently acting tubulin-binding sites.
Full text
PDF![353](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/2cfb39bac002/mbc00002-0163.png)
![354](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/75a33ea92781/mbc00002-0164.png)
![355](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/17b976b4bae1/mbc00002-0165.png)
![356](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/c9723dfcc098/mbc00002-0166.png)
![357](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/55b822871b5a/mbc00002-0167.png)
![358](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/66c464b2f6c2/mbc00002-0168.png)
![359](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/4ffe183795f9/mbc00002-0169.png)
![360](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/7fd8d3545e4b/mbc00002-0170.png)
![361](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/e8c3d0de7b49/mbc00002-0171.png)
![362](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/67d0e29c0d81/mbc00002-0172.png)
![363](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/8b98e913c552/mbc00002-0173.png)
![364](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/9e3fc40e3e10/mbc00002-0174.png)
![365](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9770/276085/472c250e445d/mbc00002-0175.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aizawa H., Emori Y., Mori A., Murofushi H., Sakai H., Suzuki K. Functional analyses of the domain structure of microtubule-associated protein-4 (MAP-U). J Biol Chem. 1991 May 25;266(15):9841–9846. [PubMed] [Google Scholar]
- Baas P. W., Pienkowski T. P., Kosik K. S. Processes induced by tau expression in Sf9 cells have an axon-like microtubule organization. J Cell Biol. 1991 Dec;115(5):1333–1344. doi: 10.1083/jcb.115.5.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biernat J., Gustke N., Drewes G., Mandelkow E. M., Mandelkow E. Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron. 1993 Jul;11(1):153–163. doi: 10.1016/0896-6273(93)90279-z. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Bramblett G. T., Goedert M., Jakes R., Merrick S. E., Trojanowski J. Q., Lee V. M. Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron. 1993 Jun;10(6):1089–1099. doi: 10.1016/0896-6273(93)90057-x. [DOI] [PubMed] [Google Scholar]
- Brandt R., Lee G. The balance between tau protein's microtubule growth and nucleation activities: implications for the formation of axonal microtubules. J Neurochem. 1993 Sep;61(3):997–1005. doi: 10.1111/j.1471-4159.1993.tb03613.x. [DOI] [PubMed] [Google Scholar]
- Butler M., Shelanski M. L. Microheterogeneity of microtubule-associated tau proteins is due to differences in phosphorylation. J Neurochem. 1986 Nov;47(5):1517–1522. doi: 10.1111/j.1471-4159.1986.tb00788.x. [DOI] [PubMed] [Google Scholar]
- Butner K. A., Kirschner M. W. Tau protein binds to microtubules through a flexible array of distributed weak sites. J Cell Biol. 1991 Nov;115(3):717–730. doi: 10.1083/jcb.115.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caceres A., Kosik K. S. Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons. Nature. 1990 Feb 1;343(6257):461–463. doi: 10.1038/343461a0. [DOI] [PubMed] [Google Scholar]
- Caceres A., Mautino J., Kosik K. S. Suppression of MAP2 in cultured cerebellar macroneurons inhibits minor neurite formation. Neuron. 1992 Oct;9(4):607–618. doi: 10.1016/0896-6273(92)90025-9. [DOI] [PubMed] [Google Scholar]
- Caceres A., Potrebic S., Kosik K. S. The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons. J Neurosci. 1991 Jun;11(6):1515–1523. doi: 10.1523/JNEUROSCI.11-06-01515.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chapin S. J., Bulinski J. C. Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau. J Cell Sci. 1991 Jan;98(Pt 1):27–36. doi: 10.1242/jcs.98.1.27. [DOI] [PubMed] [Google Scholar]
- Cleveland D. W., Hwo S. Y., Kirschner M. W. Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. J Mol Biol. 1977 Oct 25;116(2):227–247. doi: 10.1016/0022-2836(77)90214-5. [DOI] [PubMed] [Google Scholar]
- Cleveland D. W., Hwo S. Y., Kirschner M. W. Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol. 1977 Oct 25;116(2):207–225. doi: 10.1016/0022-2836(77)90213-3. [DOI] [PubMed] [Google Scholar]
- Davis A., Sage C. R., Wilson L., Farrell K. W. Purification and biochemical characterization of tubulin from the budding yeast Saccharomyces cerevisiae. Biochemistry. 1993 Aug 31;32(34):8823–8835. doi: 10.1021/bi00085a013. [DOI] [PubMed] [Google Scholar]
- Deng W. P., Nickoloff J. A. Site-directed mutagenesis of virtually any plasmid by eliminating a unique site. Anal Biochem. 1992 Jan;200(1):81–88. doi: 10.1016/0003-2697(92)90280-k. [DOI] [PubMed] [Google Scholar]
- Dhamodharan R., Wadsworth P. Modulation of microtubule dynamic instability in vivo by brain microtubule associated proteins. J Cell Sci. 1995 Apr;108(Pt 4):1679–1689. doi: 10.1242/jcs.108.4.1679. [DOI] [PubMed] [Google Scholar]
- Drechsel D. N., Hyman A. A., Cobb M. H., Kirschner M. W. Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell. 1992 Oct;3(10):1141–1154. doi: 10.1091/mbc.3.10.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drewes G., Trinczek B., Illenberger S., Biernat J., Schmitt-Ulms G., Meyer H. E., Mandelkow E. M., Mandelkow E. Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262. J Biol Chem. 1995 Mar 31;270(13):7679–7688. doi: 10.1074/jbc.270.13.7679. [DOI] [PubMed] [Google Scholar]
- Drubin D. G., Feinstein S. C., Shooter E. M., Kirschner M. W. Nerve growth factor-induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors. J Cell Biol. 1985 Nov;101(5 Pt 1):1799–1807. doi: 10.1083/jcb.101.5.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drubin D. G., Kirschner M. W. Tau protein function in living cells. J Cell Biol. 1986 Dec;103(6 Pt 2):2739–2746. doi: 10.1083/jcb.103.6.2739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ennulat D. J., Liem R. K., Hashim G. A., Shelanski M. L. Two separate 18-amino acid domains of tau promote the polymerization of tubulin. J Biol Chem. 1989 Apr 5;264(10):5327–5330. [PubMed] [Google Scholar]
- Esmaeli-Azad B., McCarty J. H., Feinstein S. C. Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability. J Cell Sci. 1994 Apr;107(Pt 4):869–879. doi: 10.1242/jcs.107.4.869. [DOI] [PubMed] [Google Scholar]
- Ferralli J., Doll T., Matus A. Sequence analysis of MAP2 function in living cells. J Cell Sci. 1994 Nov;107(Pt 11):3115–3125. doi: 10.1242/jcs.107.11.3115. [DOI] [PubMed] [Google Scholar]
- Francon J., Lennon A. M., Fellous A., Mareck A., Pierre M., Nunez J. Heterogeneity of microtubule-associated proteins and brain development. Eur J Biochem. 1982 Dec 15;129(2):465–471. doi: 10.1111/j.1432-1033.1982.tb07072.x. [DOI] [PubMed] [Google Scholar]
- Godowski P. J., Rusconi S., Miesfeld R., Yamamoto K. R. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement. Nature. 1987 Jan 22;325(6102):365–368. doi: 10.1038/325365a0. [DOI] [PubMed] [Google Scholar]
- Goedert M., Jakes R., Crowther R. A., Six J., Lübke U., Vandermeeren M., Cras P., Trojanowski J. Q., Lee V. M. The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5066–5070. doi: 10.1073/pnas.90.11.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goedert M., Jakes R. Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J. 1990 Dec;9(13):4225–4230. doi: 10.1002/j.1460-2075.1990.tb07870.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goedert M., Spillantini M. G., Jakes R., Rutherford D., Crowther R. A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989 Oct;3(4):519–526. doi: 10.1016/0896-6273(89)90210-9. [DOI] [PubMed] [Google Scholar]
- Goedert M., Spillantini M. G., Potier M. C., Ulrich J., Crowther R. A. Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J. 1989 Feb;8(2):393–399. doi: 10.1002/j.1460-2075.1989.tb03390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goode B. L., Feinstein S. C. Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau. J Cell Biol. 1994 Mar;124(5):769–782. doi: 10.1083/jcb.124.5.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gustke N., Steiner B., Mandelkow E. M., Biernat J., Meyer H. E., Goedert M., Mandelkow E. The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs. FEBS Lett. 1992 Jul 28;307(2):199–205. doi: 10.1016/0014-5793(92)80767-b. [DOI] [PubMed] [Google Scholar]
- Gustke N., Trinczek B., Biernat J., Mandelkow E. M., Mandelkow E. Domains of tau protein and interactions with microtubules. Biochemistry. 1994 Aug 16;33(32):9511–9522. doi: 10.1021/bi00198a017. [DOI] [PubMed] [Google Scholar]
- Hanemaaijer R., Ginzburg I. Involvement of mature tau isoforms in the stabilization of neurites in PC12 cells. J Neurosci Res. 1991 Sep;30(1):163–171. doi: 10.1002/jnr.490300117. [DOI] [PubMed] [Google Scholar]
- Himmler A., Drechsel D., Kirschner M. W., Martin D. W., Jr Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. Mol Cell Biol. 1989 Apr;9(4):1381–1388. doi: 10.1128/mcb.9.4.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Himmler A. Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family. Mol Cell Biol. 1989 Apr;9(4):1389–1396. doi: 10.1128/mcb.9.4.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirokawa N. Microtubule organization and dynamics dependent on microtubule-associated proteins. Curr Opin Cell Biol. 1994 Feb;6(1):74–81. doi: 10.1016/0955-0674(94)90119-8. [DOI] [PubMed] [Google Scholar]
- Hirokawa N., Shiomura Y., Okabe S. Tau proteins: the molecular structure and mode of binding on microtubules. J Cell Biol. 1988 Oct;107(4):1449–1459. doi: 10.1083/jcb.107.4.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hubbard S. R., Wei L., Ellis L., Hendrickson W. A. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature. 1994 Dec 22;372(6508):746–754. doi: 10.1038/372746a0. [DOI] [PubMed] [Google Scholar]
- Joly J. C., Flynn G., Purich D. L. The microtubule-binding fragment of microtubule-associated protein-2: location of the protease-accessible site and identification of an assembly-promoting peptide. J Cell Biol. 1989 Nov;109(5):2289–2294. doi: 10.1083/jcb.109.5.2289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Joly J. C., Purich D. L. Peptides corresponding to the second repeated sequence in MAP-2 inhibit binding of microtubule-associated proteins to microtubules. Biochemistry. 1990 Sep 25;29(38):8916–8920. doi: 10.1021/bi00490a006. [DOI] [PubMed] [Google Scholar]
- Jonsen M. D., Petersen J. M., Xu Q. P., Graves B. J. Characterization of the cooperative function of inhibitory sequences in Ets-1. Mol Cell Biol. 1996 May;16(5):2065–2073. doi: 10.1128/mcb.16.5.2065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanai Y., Chen J., Hirokawa N. Microtubule bundling by tau proteins in vivo: analysis of functional domains. EMBO J. 1992 Nov;11(11):3953–3961. doi: 10.1002/j.1460-2075.1992.tb05489.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanai Y., Takemura R., Oshima T., Mori H., Ihara Y., Yanagisawa M., Masaki T., Hirokawa N. Expression of multiple tau isoforms and microtubule bundle formation in fibroblasts transfected with a single tau cDNA. J Cell Biol. 1989 Sep;109(3):1173–1184. doi: 10.1083/jcb.109.3.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanemaru K., Takio K., Miura R., Titani K., Ihara Y. Fetal-type phosphorylation of the tau in paired helical filaments. J Neurochem. 1992 May;58(5):1667–1675. doi: 10.1111/j.1471-4159.1992.tb10039.x. [DOI] [PubMed] [Google Scholar]
- Knops J., Kosik K. S., Lee G., Pardee J. D., Cohen-Gould L., McConlogue L. Overexpression of tau in a nonneuronal cell induces long cellular processes. J Cell Biol. 1991 Aug;114(4):725–733. doi: 10.1083/jcb.114.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kosik K. S., McConlogue L. Microtubule-associated protein function: lessons from expression in Spodoptera frugiperda cells. Cell Motil Cytoskeleton. 1994;28(3):195–198. doi: 10.1002/cm.970280302. [DOI] [PubMed] [Google Scholar]
- Kosik K. S., Orecchio L. D., Bakalis S., Neve R. L. Developmentally regulated expression of specific tau sequences. Neuron. 1989 Apr;2(4):1389–1397. doi: 10.1016/0896-6273(89)90077-9. [DOI] [PubMed] [Google Scholar]
- Larcher J. C., Boucher D., Ginzburg I., Gros F., Denoulet P. Heterogeneity of Tau proteins during mouse brain development and differentiation of cultured neurons. Dev Biol. 1992 Nov;154(1):195–204. doi: 10.1016/0012-1606(92)90059-p. [DOI] [PubMed] [Google Scholar]
- Lee G., Cowan N., Kirschner M. The primary structure and heterogeneity of tau protein from mouse brain. Science. 1988 Jan 15;239(4837):285–288. doi: 10.1126/science.3122323. [DOI] [PubMed] [Google Scholar]
- Lee G., Neve R. L., Kosik K. S. The microtubule binding domain of tau protein. Neuron. 1989 Jun;2(6):1615–1624. doi: 10.1016/0896-6273(89)90050-0. [DOI] [PubMed] [Google Scholar]
- Lee G. Non-motor microtubule-associated proteins. Curr Opin Cell Biol. 1993 Feb;5(1):88–94. doi: 10.1016/s0955-0674(05)80013-4. [DOI] [PubMed] [Google Scholar]
- Lee G., Rook S. L. Expression of tau protein in non-neuronal cells: microtubule binding and stabilization. J Cell Sci. 1992 Jun;102(Pt 2):227–237. doi: 10.1242/jcs.102.2.227. [DOI] [PubMed] [Google Scholar]
- Lefstin J. A., Thomas J. R., Yamamoto K. R. Influence of a steroid receptor DNA-binding domain on transcriptional regulatory functions. Genes Dev. 1994 Dec 1;8(23):2842–2856. doi: 10.1101/gad.8.23.2842. [DOI] [PubMed] [Google Scholar]
- Lewis S. A., Cowan N. Microtubule bundling. Nature. 1990 Jun 21;345(6277):674–674. doi: 10.1038/345674a0. [DOI] [PubMed] [Google Scholar]
- Lewis S. A., Ivanov I. E., Lee G. H., Cowan N. J. Organization of microtubules in dendrites and axons is determined by a short hydrophobic zipper in microtubule-associated proteins MAP2 and tau. Nature. 1989 Nov 30;342(6249):498–505. doi: 10.1038/342498a0. [DOI] [PubMed] [Google Scholar]
- Lewis S. A., Wang D. H., Cowan N. J. Microtubule-associated protein MAP2 shares a microtubule binding motif with tau protein. Science. 1988 Nov 11;242(4880):936–939. doi: 10.1126/science.3142041. [DOI] [PubMed] [Google Scholar]
- Lichtenberg-Kraag B., Mandelkow E. M., Biernat J., Steiner B., Schröter C., Gustke N., Meyer H. E., Mandelkow E. Phosphorylation-dependent epitopes of neurofilament antibodies on tau protein and relationship with Alzheimer tau. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5384–5388. doi: 10.1073/pnas.89.12.5384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindwall G., Cole R. D. Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem. 1984 Apr 25;259(8):5301–5305. [PubMed] [Google Scholar]
- Léger J. G., Brandt R., Lee G. Identification of tau protein regions required for process formation in PC12 cells. J Cell Sci. 1994 Dec;107(Pt 12):3403–3412. doi: 10.1242/jcs.107.12.3403. [DOI] [PubMed] [Google Scholar]
- Mandelkow E. M., Mandelkow E. Tau as a marker for Alzheimer's disease. Trends Biochem Sci. 1993 Dec;18(12):480–483. doi: 10.1016/0968-0004(93)90011-b. [DOI] [PubMed] [Google Scholar]
- Mandelkow E., Mandelkow E. M. Microtubules and microtubule-associated proteins. Curr Opin Cell Biol. 1995 Feb;7(1):72–81. doi: 10.1016/0955-0674(95)80047-6. [DOI] [PubMed] [Google Scholar]
- Mareck A., Fellous A., Francon J., Nunez J. Changes in composition and activity of microtubule-associated proteins during brain development. Nature. 1980 Mar 27;284(5754):353–355. doi: 10.1038/284353a0. [DOI] [PubMed] [Google Scholar]
- Mitchison T., Kirschner M. Microtubule assembly nucleated by isolated centrosomes. Nature. 1984 Nov 15;312(5991):232–237. doi: 10.1038/312232a0. [DOI] [PubMed] [Google Scholar]
- Oblinger M. M., Argasinski A., Wong J., Kosik K. S. Tau gene expression in rat sensory neurons during development and regeneration. J Neurosci. 1991 Aug;11(8):2453–2459. doi: 10.1523/JNEUROSCI.11-08-02453.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Panda D., Goode B. L., Feinstein S. C., Wilson L. Kinetic stabilization of microtubule dynamics at steady state by tau and microtubule-binding domains of tau. Biochemistry. 1995 Sep 5;34(35):11117–11127. doi: 10.1021/bi00035a017. [DOI] [PubMed] [Google Scholar]
- Pryer N. K., Walker R. A., Skeen V. P., Bourns B. D., Soboeiro M. F., Salmon E. D. Brain microtubule-associated proteins modulate microtubule dynamic instability in vitro. Real-time observations using video microscopy. J Cell Sci. 1992 Dec;103(Pt 4):965–976. doi: 10.1242/jcs.103.4.965. [DOI] [PubMed] [Google Scholar]
- Schoenfeld T. A., Obar R. A. Diverse distribution and function of fibrous microtubule-associated proteins in the nervous system. Int Rev Cytol. 1994;151:67–137. doi: 10.1016/s0074-7696(08)62631-5. [DOI] [PubMed] [Google Scholar]
- Schweers O., Schönbrunn-Hanebeck E., Marx A., Mandelkow E. Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem. 1994 Sep 30;269(39):24290–24297. [PubMed] [Google Scholar]
- Shea T. B., Beermann M. L., Nixon R. A., Fischer I. Microtubule-associated protein tau is required for axonal neurite elaboration by neuroblastoma cells. J Neurosci Res. 1992 Jul;32(3):363–374. doi: 10.1002/jnr.490320308. [DOI] [PubMed] [Google Scholar]
- Soderling T. R. Protein kinases. Regulation by autoinhibitory domains. J Biol Chem. 1990 Feb 5;265(4):1823–1826. [PubMed] [Google Scholar]
- Takemura R., Okabe S., Umeyama T., Kanai Y., Cowan N. J., Hirokawa N. Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B, MAP2 or tau. J Cell Sci. 1992 Dec;103(Pt 4):953–964. doi: 10.1242/jcs.103.4.953. [DOI] [PubMed] [Google Scholar]
- Trinczek B., Biernat J., Baumann K., Mandelkow E. M., Mandelkow E. Domains of tau protein, differential phosphorylation, and dynamic instability of microtubules. Mol Biol Cell. 1995 Dec;6(12):1887–1902. doi: 10.1091/mbc.6.12.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trojanowski J. Q., Lee V. M. Paired helical filament tau in Alzheimer's disease. The kinase connection. Am J Pathol. 1994 Mar;144(3):449–453. [PMC free article] [PubMed] [Google Scholar]
- Weingarten M. D., Lockwood A. H., Hwo S. Y., Kirschner M. W. A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A. 1975 May;72(5):1858–1862. doi: 10.1073/pnas.72.5.1858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- West R. R., Tenbarge K. M., Olmsted J. B. A model for microtubule-associated protein 4 structure. Domains defined by comparisons of human, mouse, and bovine sequences. J Biol Chem. 1991 Nov 15;266(32):21886–21896. [PubMed] [Google Scholar]
- Wiche G., Oberkanins C., Himmler A. Molecular structure and function of microtubule-associated proteins. Int Rev Cytol. 1991;124:217–273. doi: 10.1016/s0074-7696(08)61528-4. [DOI] [PubMed] [Google Scholar]
- Wille H., Drewes G., Biernat J., Mandelkow E. M., Mandelkow E. Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J Cell Biol. 1992 Aug;118(3):573–584. doi: 10.1083/jcb.118.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]