Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1988 Oct 1;107(4):1449–1459. doi: 10.1083/jcb.107.4.1449

Tau proteins: the molecular structure and mode of binding on microtubules

PMCID: PMC2115262  PMID: 3139677

Abstract

Tau is a family of closely related proteins (55,000-62,000 mol wt) which are contained in the nerve cells and copolymerize with tubulin to induce the formation of microtubules in vitro. All information so far has indicated that tau is closely apposed to the microtubule lattice, and there was no indication of domains projecting from the microtubule polymer lattice. We have studied the molecular structure of the tau factor and its mode of binding on microtubules using the quick-freeze, deep-etch method (QF.DE) and low angle rotary shadowing technique. Phosphocellulose column-purified tubulin from porcine brain was polymerized with tau and the centrifuged pellets were processed by QF.DE. We observed periodic armlike elements (18.7 +/- 4.8 nm long) projecting from the microtubule surface. Most of the projections appeared to cross-link adjacent microtubules. We measured the longitudinal periodicity of tau projections on the microtubules and found it to match the 6-dimer pattern better than the 12-dimer pattern. The stoichiometry of tau versus tubulin in preparations of tau saturated microtubules was 1:approximately 5.0 (molar ratio). Tau molecules adsorbed on mica took on rodlike forms (56.1 +/- 14.1 nm long). Although both tau and MAP1 are contained in axons, competitive binding studies demonstrated that the binding sites of tau and MAP1A on the microtubule surfaces are most distinct, although they may partially overlap.

Full Text

The Full Text of this article is available as a PDF (4.0 MB).

Selected References

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

  1. Aizawa H., Murofushi H., Kotani S., Hisanaga S., Hirokawa N., Sakai H. Limited chymotryptic digestion of bovine adrenal 190,000-Mr microtubule-associated protein and preparation of a 27,000-Mr fragment which stimulates microtubule assembly. J Biol Chem. 1987 Mar 15;262(8):3782–3787. [PubMed] [Google Scholar]
  2. Amos L. A. Arrangement of high molecular weight associated proteins on purified mammalian brain microtubules. J Cell Biol. 1977 Mar;72(3):642–654. doi: 10.1083/jcb.72.3.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bloom G. S., Schoenfeld T. A., Vallee R. B. Widespread distribution of the major polypeptide component of MAP 1 (microtubule-associated protein 1) in the nervous system. J Cell Biol. 1984 Jan;98(1):320–330. doi: 10.1083/jcb.98.1.320. [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. 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]
  7. 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]
  8. Grundke-Iqbal I., Iqbal K., Quinlan M., Tung Y. C., Zaidi M. S., Wisniewski H. M. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986 May 5;261(13):6084–6089. [PubMed] [Google Scholar]
  9. Heuser J. E., Kirschner M. W. Filament organization revealed in platinum replicas of freeze-dried cytoskeletons. J Cell Biol. 1980 Jul;86(1):212–234. doi: 10.1083/jcb.86.1.212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heuser J. E., Salpeter S. R. Organization of acetylcholine receptors in quick-frozen, deep-etched, and rotary-replicated Torpedo postsynaptic membrane. J Cell Biol. 1979 Jul;82(1):150–173. doi: 10.1083/jcb.82.1.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirokawa N. 270K microtubule-associated protein cross-reacting with anti-MAP2 IgG in the crayfish peripheral nerve axon. J Cell Biol. 1986 Jul;103(1):33–39. doi: 10.1083/jcb.103.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirokawa N., Bloom G. S., Vallee R. B. Cytoskeletal architecture and immunocytochemical localization of microtubule-associated proteins in regions of axons associated with rapid axonal transport: the beta,beta'-iminodipropionitrile-intoxicated axon as a model system. J Cell Biol. 1985 Jul;101(1):227–239. doi: 10.1083/jcb.101.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hirokawa N. Cross-linker system between neurofilaments, microtubules, and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method. J Cell Biol. 1982 Jul;94(1):129–142. doi: 10.1083/jcb.94.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hirokawa N., Hisanaga S. "Buttonin," a unique button-shaped microtubule-associated protein (75 kD) that decorates spindle microtubule surface hexagonally. J Cell Biol. 1987 Jun;104(6):1553–1561. doi: 10.1083/jcb.104.6.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hirokawa N., Takemura R., Hisanaga S. Cytoskeletal architecture of isolated mitotic spindle with special reference to microtubule-associated proteins and cytoplasmic dynein. J Cell Biol. 1985 Nov;101(5 Pt 1):1858–1870. doi: 10.1083/jcb.101.5.1858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huber G., Matus A. Immunocytochemical localization of microtubule-associated protein 1 in rat cerebellum using monoclonal antibodies. J Cell Biol. 1984 Feb;98(2):777–781. doi: 10.1083/jcb.98.2.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. ITZHAKI R. F., GILL D. M. A MICRO-BIURET METHOD FOR ESTIMATING PROTEINS. Anal Biochem. 1964 Dec;9:401–410. doi: 10.1016/0003-2697(64)90200-3. [DOI] [PubMed] [Google Scholar]
  18. Ihara Y., Nukina N., Miura R., Ogawara M. Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer's disease. J Biochem. 1986 Jun;99(6):1807–1810. doi: 10.1093/oxfordjournals.jbchem.a135662. [DOI] [PubMed] [Google Scholar]
  19. Jensen C. G., Smaill B. H. Analysis of the spatial organization of microtubule-associated proteins. J Cell Biol. 1986 Aug;103(2):559–569. doi: 10.1083/jcb.103.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kim H., Binder L. I., Rosenbaum J. L. The periodic association of MAP2 with brain microtubules in vitro. J Cell Biol. 1979 Feb;80(2):266–276. doi: 10.1083/jcb.80.2.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kim H., Jensen C. G., Rebhun L. I. The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure. Ann N Y Acad Sci. 1986;466:218–239. doi: 10.1111/j.1749-6632.1986.tb38396.x. [DOI] [PubMed] [Google Scholar]
  22. Kosik K. S., Joachim C. L., Selkoe D. J. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4044–4048. doi: 10.1073/pnas.83.11.4044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Matus A., Huber G., Bernhardt R. Neuronal microdifferentiation. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):775–782. doi: 10.1101/sqb.1983.048.01.079. [DOI] [PubMed] [Google Scholar]
  25. Murofushi H., Kotani S., Aizawa H., Hisanaga S., Hirokawa N., Sakai H. Purification and characterization of a 190-kD microtubule-associated protein from bovine adrenal cortex. J Cell Biol. 1986 Nov;103(5):1911–1919. doi: 10.1083/jcb.103.5.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murphy D. B., Borisy G. G. Association of high-molecular-weight proteins with microtubules and their role in microtubule assembly in vitro. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2696–2700. doi: 10.1073/pnas.72.7.2696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Olmsted J. B. Microtubule-associated proteins. Annu Rev Cell Biol. 1986;2:421–457. doi: 10.1146/annurev.cb.02.110186.002225. [DOI] [PubMed] [Google Scholar]
  28. Serrano L., Montejo de Garcini E., Hernández M. A., Avila J. Localization of the tubulin binding site for tau protein. Eur J Biochem. 1985 Dec 16;153(3):595–600. doi: 10.1111/j.1432-1033.1985.tb09342.x. [DOI] [PubMed] [Google Scholar]
  29. Shelanski M. L., Gaskin F., Cantor C. R. Microtubule assembly in the absence of added nucleotides. Proc Natl Acad Sci U S A. 1973 Mar;70(3):765–768. doi: 10.1073/pnas.70.3.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shiomura Y., Hirokawa N. The molecular structure of microtubule-associated protein 1A (MAP1A) in vivo and in vitro. An immunoelectron microscopy and quick-freeze, deep-etch study. J Neurosci. 1987 May;7(5):1461–1469. doi: 10.1523/JNEUROSCI.07-05-01461.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sloboda R. D., Rudolph S. A., Rosenbaum J. L., Greengard P. Cyclic AMP-dependent endogenous phosphorylation of a microtubule-associated protein. Proc Natl Acad Sci U S A. 1975 Jan;72(1):177–181. doi: 10.1073/pnas.72.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sobue K., Fujita M., Muramoto Y., Kakiuchi S. The calmodulin-binding protein in microtubules is tau factor. FEBS Lett. 1981 Sep 14;132(1):137–140. doi: 10.1016/0014-5793(81)80447-4. [DOI] [PubMed] [Google Scholar]
  33. Tyler J. M., Branton D. Rotary shadowing of extended molecules dried from glycerol. J Ultrastruct Res. 1980 May;71(2):95–102. doi: 10.1016/s0022-5320(80)90098-2. [DOI] [PubMed] [Google Scholar]
  34. Vallee R. B. A taxol-dependent procedure for the isolation of microtubules and microtubule-associated proteins (MAPs). J Cell Biol. 1982 Feb;92(2):435–442. doi: 10.1083/jcb.92.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vallee R. B., Davis S. E. Low molecular weight microtubule-associated proteins are light chains of microtubule-associated protein 1 (MAP 1). Proc Natl Acad Sci U S A. 1983 Mar;80(5):1342–1346. doi: 10.1073/pnas.80.5.1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vallee R. Structure and phosphorylation of microtubule-associated protein 2 (MAP 2). Proc Natl Acad Sci U S A. 1980 Jun;77(6):3206–3210. doi: 10.1073/pnas.77.6.3206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Voter W. A., Erickson H. P. Electron microscopy of MAP 2 (microtubule-associated protein 2). J Ultrastruct Res. 1982 Sep;80(3):374–382. doi: 10.1016/s0022-5320(82)80051-8. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Zingsheim H. P., Herzog W., Weber K. Differences in surface morphology of microtubules reconstituted from pure brain tubulin using two different microtubule-associated proteins: the high molecular weight MAP 2 proteins and tau proteins. Eur J Cell Biol. 1979 Jun;19(2):175–183. [PubMed] [Google Scholar]
  40. de la Torre J., Carrascosa J. L., Avila J. The localization of tau proteins on the microtubule surface. Eur J Cell Biol. 1986 Apr;40(2):233–237. [PubMed] [Google Scholar]

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

RESOURCES