Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1995 Dec 1;131(5):1327–1340. doi: 10.1083/jcb.131.5.1327

Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain

PMCID: PMC2120645  PMID: 8522593

Abstract

The neuronal microtubule-associated protein tau is required for the development of cell polarity in cultured neurons. Using PC12 cells that stably express tau and tau amino-terminal fragments, we report that tau interacts with the neural plasma membrane through its amino-terminal projection domain. In differentiated PC12 transfectants, tau is found in growth cone-like structures in a nonmicrotubule-dependent manner. In hippocampal neurons, tau is differentially extracted by detergent and enriched in the growth cone and the distal axon when membrane is left intact. In PC12 transfectants, overexpression of tau's amino-terminal fragment, but not of full-length tau, suppresses NGF-induced process formation. Our data suggest that tau's amino-terminal projection domain has an important role in neuritic development and establishes tau as a mediator of microtubule-plasma membrane interactions.

Full Text

The Full Text of this article is available as a PDF (4.7 MB).

Selected References

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

  1. 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]
  2. Bottenstein J. E., Sato G. H. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979 Jan;76(1):514–517. doi: 10.1073/pnas.76.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brandt R., Lee G. Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. J Biol Chem. 1993 Feb 15;268(5):3414–3419. [PubMed] [Google Scholar]
  5. Brion J. P., Guilleminot J., Couchie D., Flament-Durand J., Nunez J. Both adult and juvenile tau microtubule-associated proteins are axon specific in the developing and adult rat cerebellum. Neuroscience. 1988 Apr;25(1):139–146. doi: 10.1016/0306-4522(88)90013-9. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Carlier M. F., Simon C., Cassoly R., Pradel L. A. Interaction between microtubule-associated protein tau and spectrin. Biochimie. 1984 Apr;66(4):305–311. doi: 10.1016/0300-9084(84)90007-5. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Correas I., Padilla R., Avila J. The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding. Biochem J. 1990 Jul 1;269(1):61–64. doi: 10.1042/bj2690061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. DiTella M., Feiguin F., Morfini G., Cáceres A. Microfilament-associated growth cone component depends upon Tau for its intracellular localization. Cell Motil Cytoskeleton. 1994;29(2):117–130. doi: 10.1002/cm.970290204. [DOI] [PubMed] [Google Scholar]
  14. Dotti C. G., Banker G. A., Binder L. I. The expression and distribution of the microtubule-associated proteins tau and microtubule-associated protein 2 in hippocampal neurons in the rat in situ and in cell culture. Neuroscience. 1987 Oct;23(1):121–130. doi: 10.1016/0306-4522(87)90276-4. [DOI] [PubMed] [Google Scholar]
  15. Dotti C. G., Sullivan C. A., Banker G. A. The establishment of polarity by hippocampal neurons in culture. J Neurosci. 1988 Apr;8(4):1454–1468. doi: 10.1523/JNEUROSCI.08-04-01454.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. 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]
  19. Ferreira A., Busciglio J., Cáceres A. Microtubule formation and neurite growth in cerebellar macroneurons which develop in vitro: evidence for the involvement of the microtubule-associated proteins, MAP-1a, HMW-MAP2 and Tau. Brain Res Dev Brain Res. 1989 Oct 1;49(2):215–228. doi: 10.1016/0165-3806(89)90023-0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Griffith L. M., Pollard T. D. Evidence for actin filament-microtubule interaction mediated by microtubule-associated proteins. J Cell Biol. 1978 Sep;78(3):958–965. doi: 10.1083/jcb.78.3.958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Griffith L. M., Pollard T. D. The interaction of actin filaments with microtubules and microtubule-associated proteins. J Biol Chem. 1982 Aug 10;257(15):9143–9151. [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Harada A., Oguchi K., Okabe S., Kuno J., Terada S., Ohshima T., Sato-Yoshitake R., Takei Y., Noda T., Hirokawa N. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. 1994 Jun 9;369(6480):488–491. doi: 10.1038/369488a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Kanai Y., Hirokawa N. Sorting mechanisms of tau and MAP2 in neurons: suppressed axonal transit of MAP2 and locally regulated microtubule binding. Neuron. 1995 Feb;14(2):421–432. doi: 10.1016/0896-6273(95)90298-8. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Kosik K. S., Orecchio L. D., Binder L., Trojanowski J. Q., Lee V. M., Lee G. Epitopes that span the tau molecule are shared with paired helical filaments. Neuron. 1988 Nov;1(9):817–825. doi: 10.1016/0896-6273(88)90129-8. [DOI] [PubMed] [Google Scholar]
  32. Kowall N. W., Kosik K. S. Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease. Ann Neurol. 1987 Nov;22(5):639–643. doi: 10.1002/ana.410220514. [DOI] [PubMed] [Google Scholar]
  33. Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Litman P., Barg J., Rindzoonski L., Ginzburg I. Subcellular localization of tau mRNA in differentiating neuronal cell culture: implications for neuronal polarity. Neuron. 1993 Apr;10(4):627–638. doi: 10.1016/0896-6273(93)90165-n. [DOI] [PubMed] [Google Scholar]
  37. Loomis P. A., Howard T. H., Castleberry R. P., Binder L. I. Identification of nuclear tau isoforms in human neuroblastoma cells. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8422–8426. doi: 10.1073/pnas.87.21.8422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lu Q., Wood J. G. Characterization of fluorescently derivatized bovine tau protein and its localization and functions in cultured Chinese hamster ovary cells. Cell Motil Cytoskeleton. 1993;25(2):190–200. doi: 10.1002/cm.970250208. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Mitchison T., Kirschner M. Cytoskeletal dynamics and nerve growth. Neuron. 1988 Nov;1(9):761–772. doi: 10.1016/0896-6273(88)90124-9. [DOI] [PubMed] [Google Scholar]
  41. Nakata T., Hirokawa N. Cytoskeletal reorganization of human platelets after stimulation revealed by the quick-freeze deep-etch technique. J Cell Biol. 1987 Oct;105(4):1771–1780. doi: 10.1083/jcb.105.4.1771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Papasozomenos S. C., Binder L. I. Phosphorylation determines two distinct species of Tau in the central nervous system. Cell Motil Cytoskeleton. 1987;8(3):210–226. doi: 10.1002/cm.970080303. [DOI] [PubMed] [Google Scholar]
  43. Pfeffer S. R., Drubin D. G., Kelly R. B. Identification of three coated vesicle components as alpha- and beta-tubulin linked to a phosphorylated 50,000-dalton polypeptide. J Cell Biol. 1983 Jul;97(1):40–47. doi: 10.1083/jcb.97.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Prickett K. S., Amberg D. C., Hopp T. P. A calcium-dependent antibody for identification and purification of recombinant proteins. Biotechniques. 1989 Jun;7(6):580–589. [PubMed] [Google Scholar]
  45. Rendon A., Jung D., Jancsik V. Interaction of microtubules and microtubule-associated proteins (MAPs) with rat brain mitochondria. Biochem J. 1990 Jul 15;269(2):555–556. doi: 10.1042/bj2690555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rodriguez-Boulan E., Powell S. K. Polarity of epithelial and neuronal cells. Annu Rev Cell Biol. 1992;8:395–427. doi: 10.1146/annurev.cb.08.110192.002143. [DOI] [PubMed] [Google Scholar]
  47. Sattilaro R. F., Dentler W. L., LeCluyse E. L. Microtubule-associated proteins (MAPs) and the organization of actin filaments in vitro. J Cell Biol. 1981 Aug;90(2):467–473. doi: 10.1083/jcb.90.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Selden S. C., Pollard T. D. Phosphorylation of microtubule-associated proteins regulates their interaction with actin filaments. J Biol Chem. 1983 Jun 10;258(11):7064–7071. [PubMed] [Google Scholar]
  49. Tanaka E. M., Kirschner M. W. Microtubule behavior in the growth cones of living neurons during axon elongation. J Cell Biol. 1991 Oct;115(2):345–363. doi: 10.1083/jcb.115.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tanaka E., Ho T., Kirschner M. W. The role of microtubule dynamics in growth cone motility and axonal growth. J Cell Biol. 1995 Jan;128(1-2):139–155. doi: 10.1083/jcb.128.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Trojanowski J. Q., Schuck T., Schmidt M. L., Lee V. M. Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem. 1989 Feb;37(2):209–215. doi: 10.1177/37.2.2492045. [DOI] [PubMed] [Google Scholar]
  52. Tucker R. P. The roles of microtubule-associated proteins in brain morphogenesis: a review. Brain Res Brain Res Rev. 1990 May-Aug;15(2):101–120. doi: 10.1016/0165-0173(90)90013-e. [DOI] [PubMed] [Google Scholar]
  53. Wiedenmann B., Lawley K., Grund C., Branton D. Solubilization of proteins from bovine brain coated vesicles by protein perturbants and Triton X-100. J Cell Biol. 1985 Jul;101(1):12–18. doi: 10.1083/jcb.101.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES