Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1994 Mar 1;124(5):769–782. doi: 10.1083/jcb.124.5.769

Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau

PMCID: PMC2119949  PMID: 8120098

Abstract

Tau is a developmentally regulated microtubule-associated protein that influences microtubule behavior by directly associating with tubulin. The carboxyl terminus of tau contains multiple 18-amino acid repeats that bind microtubules and are separated by 13-14-amino acid inter- repeat (IR) regions previously thought to function as "linkers." Here, we have performed a high resolution deletion analysis of tau and identified the IR region located between repeats 1 and 2 (the R1-R2 IR) as a unique microtubule binding site with more than twice the binding affinity of any individual repeat. Truncation analyses and site- directed mutagenesis reveal that the binding activity of this site is derived primarily from lys265 and lys272, with a lesser contribution from lys271. These results predict strong, discrete electrostatic interactions between the R1-R2 IR and tubulin, in contrast to the distributed array of weak interactions thought to underlie the association between 18-amino acid repeats and microtubules (Butner, K. A., and M. W. Kirschner. J. Cell Biol. 115:717-730). Moreover, competition assays suggest that the R1-R2 IR associates with microtubules at tubulin site(s) distinct from those bound by the repeats. Finally, a synthetic peptide corresponding to just 10 amino acids of the R1-R2 IR is sufficient to promote tubulin polymerization in a sequence-dependent manner. Since the R1-R2 IR is specifically expressed in adult tau, its action may underlie some of the developmental transitions observed in neuronal microtubule organization. We suggest that the R1-R2 IR may establish an adult- specific, high affinity anchor that tethers the otherwise mobile tau molecule to the tubulin lattice, thereby increasing microtubule stability. Moreover, the absence of R1-R2 IR expression during early development may allow for the cytoskeletal plasticity required of immature neurons.

Full Text

The Full Text of this article is available as a PDF (2.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. 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]
  3. Biernat J., Mandelkow E. M., Schröter C., Lichtenberg-Kraag B., Steiner B., Berling B., Meyer H., Mercken M., Vandermeeren A., Goedert M. The switch of tau protein to an Alzheimer-like state includes the phosphorylation of two serine-proline motifs upstream of the microtubule binding region. EMBO J. 1992 Apr;11(4):1593–1597. doi: 10.1002/j.1460-2075.1992.tb05204.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Binder L. I., Frankfurter A., Rebhun L. I. The distribution of tau in the mammalian central nervous system. J Cell Biol. 1985 Oct;101(4):1371–1378. doi: 10.1083/jcb.101.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. Chen J., Kanai Y., Cowan N. J., Hirokawa N. Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons. Nature. 1992 Dec 17;360(6405):674–677. doi: 10.1038/360674a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Couchie D., Mavilia C., Georgieff I. S., Liem R. K., Shelanski M. L., Nunez J. Primary structure of high molecular weight tau present in the peripheral nervous system. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4378–4381. doi: 10.1073/pnas.89.10.4378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Couchie D., Nunez J. Immunological characterization of microtubule-associated proteins specific for the immature brain. FEBS Lett. 1985 Sep 2;188(2):331–335. doi: 10.1016/0014-5793(85)80397-5. [DOI] [PubMed] [Google Scholar]
  17. Cross D., Dominguez J., Maccioni R. B., Avila J. MAP-1 and MAP-2 binding sites at the C-terminus of beta-tubulin. Studies with synthetic tubulin peptides. Biochemistry. 1991 Apr 30;30(17):4362–4366. doi: 10.1021/bi00231a036. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Drewes G., Lichtenberg-Kraag B., Döring F., Mandelkow E. M., Biernat J., Goris J., Dorée M., Mandelkow E. Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state. EMBO J. 1992 Jun;11(6):2131–2138. doi: 10.1002/j.1460-2075.1992.tb05272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Drubin D. G., Caput D., Kirschner M. W. Studies on the expression of the microtubule-associated protein, tau, during mouse brain development, with newly isolated complementary DNA probes. J Cell Biol. 1984 Mar;98(3):1090–1097. doi: 10.1083/jcb.98.3.1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Drubin D., Kobayashi S., Kellogg D., Kirschner M. Regulation of microtubule protein levels during cellular morphogenesis in nerve growth factor-treated PC12 cells. J Cell Biol. 1988 May;106(5):1583–1591. doi: 10.1083/jcb.106.5.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Drubin D., Kobayashi S., Kirschner M. Association of tau protein with microtubules in living cells. Ann N Y Acad Sci. 1986;466:257–268. doi: 10.1111/j.1749-6632.1986.tb38398.x. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Farías G. A., Vial C., Maccioni R. B. Specific macromolecular interactions between tau and the microtubule system. Mol Cell Biochem. 1992 May 13;112(1):81–88. doi: 10.1007/BF00229646. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Gaskin F., Cantor C. R., Shelanski M. L. Turbidimetric studies of the in vitro assembly and disassembly of porcine neurotubules. J Mol Biol. 1974 Nov 15;89(4):737–755. doi: 10.1016/0022-2836(74)90048-5. [DOI] [PubMed] [Google Scholar]
  30. Georgieff I. S., Liem R. K., Mellado W., Nunez J., Shelanski M. L. High molecular weight tau: preferential localization in the peripheral nervous system. J Cell Sci. 1991 Sep;100(Pt 1):55–60. doi: 10.1242/jcs.100.1.55. [DOI] [PubMed] [Google Scholar]
  31. Ginzburg I., Scherson T., Giveon D., Behar L., Littauer U. Z. Modulation of mRNA for microtubule-associated proteins during brain development. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4892–4896. doi: 10.1073/pnas.79.16.4892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Goedert M., Cohen E. S., 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 [corrected]. FEBS Lett. 1992 Nov 2;312(1):95–99. doi: 10.1016/0014-5793(92)81418-l. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Goedert M., Spillantini M. G., Crowther R. A. Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1983–1987. doi: 10.1073/pnas.89.5.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Goode B. L., Feinstein S. C. "Speedprep" purification of template for double-stranded DNA sequencing. Biotechniques. 1992 Mar;12(3):374–375. [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Hasegawa M., Morishima-Kawashima M., Takio K., Suzuki M., Titani K., Ihara Y. Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain. J Biol Chem. 1992 Aug 25;267(24):17047–17054. [PubMed] [Google Scholar]
  42. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  43. Hill T. L., Carlier M. F. Steady-state theory of the interference of GTP hydrolysis in the mechanism of microtubule assembly. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7234–7238. doi: 10.1073/pnas.80.23.7234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. 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]
  47. Ishiguro K., Takamatsu M., Tomizawa K., Omori A., Takahashi M., Arioka M., Uchida T., Imahori K. Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments. J Biol Chem. 1992 May 25;267(15):10897–10901. [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. 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]
  51. 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]
  52. Kosik K. S., Caceres A. Tau protein and the establishment of an axonal morphology. J Cell Sci Suppl. 1991;15:69–74. doi: 10.1242/jcs.1991.supplement_15.10. [DOI] [PubMed] [Google Scholar]
  53. 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]
  54. Ksiezak-Reding H., Liu W. K., Yen S. H. Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments. Brain Res. 1992 Dec 4;597(2):209–219. doi: 10.1016/0006-8993(92)91476-u. [DOI] [PubMed] [Google Scholar]
  55. 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]
  56. 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]
  57. 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]
  58. Lewis S. A., Cowan N. Microtubule bundling. Nature. 1990 Jun 21;345(6277):674–674. doi: 10.1038/345674a0. [DOI] [PubMed] [Google Scholar]
  59. 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]
  60. Littauer U. Z., Giveon D., Thierauf M., Ginzburg I., Ponstingl H. Common and distinct tubulin binding sites for microtubule-associated proteins. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7162–7166. doi: 10.1073/pnas.83.19.7162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Ludueña R. F. Are tubulin isotypes functionally significant. Mol Biol Cell. 1993 May;4(5):445–457. doi: 10.1091/mbc.4.5.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Maccioni R. B., Rivas C. I., Vera J. C. Differential interaction of synthetic peptides from the carboxyl-terminal regulatory domain of tubulin with microtubule-associated proteins. EMBO J. 1988 Jul;7(7):1957–1963. doi: 10.1002/j.1460-2075.1988.tb03033.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Mandelkow E. M., Drewes G., Biernat J., Gustke N., Van Lint J., Vandenheede J. R., Mandelkow E. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett. 1992 Dec 21;314(3):315–321. doi: 10.1016/0014-5793(92)81496-9. [DOI] [PubMed] [Google Scholar]
  64. 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]
  65. 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]
  66. Nukina N., Kosik K. S., Selkoe D. J. Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein. Proc Natl Acad Sci U S A. 1987 May;84(10):3415–3419. doi: 10.1073/pnas.84.10.3415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. 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]
  68. Scott C. W., Klika A. B., Lo M. M., Norris T. E., Caputo C. B. Tau protein induces bundling of microtubules in vitro: comparison of different tau isoforms and a tau protein fragment. J Neurosci Res. 1992 Sep;33(1):19–29. doi: 10.1002/jnr.490330104. [DOI] [PubMed] [Google Scholar]
  69. Serrano L., Avila J., Maccioni R. B. Controlled proteolysis of tubulin by subtilisin: localization of the site for MAP2 interaction. Biochemistry. 1984 Sep 25;23(20):4675–4681. doi: 10.1021/bi00315a024. [DOI] [PubMed] [Google Scholar]
  70. Serrano L., de la Torre J., Maccioni R. B., Avila J. Involvement of the carboxyl-terminal domain of tubulin in the regulation of its assembly. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5989–5993. doi: 10.1073/pnas.81.19.5989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. 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]
  72. Vulliet R., Halloran S. M., Braun R. K., Smith A. J., Lee G. Proline-directed phosphorylation of human Tau protein. J Biol Chem. 1992 Nov 5;267(31):22570–22574. [PubMed] [Google Scholar]
  73. 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]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES