Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1984 Apr 1;98(4):1355–1362. doi: 10.1083/jcb.98.4.1355

Inhibition of neurite initiation and growth by taxol

PMCID: PMC2113225  PMID: 6143759

Abstract

We cultured sensory neurons from chick embryos in media containing the alkaloid taxol at concentrations from 7 X 10(-9) to 3.5 X 10(-6) M. When plated at taxol concentrations above 7 X 10(-8) M for 24 h, neurons have short broad extensions that do not elongate on the culture substratum. When actively growing neurites are exposed to these levels of taxol, neurite growth stops immediately and does not recommence. The broad processes of neurons cultured 24 h with taxol contain densely packed arrays of microtubules that loop back at the ends of the process. Neurofilaments are segregated from microtubules into bundles and tangled masses in these taxol-treated neurons. At the ends of neurites treated for 5 min with taxol, microtubules also turn and loop back abnormally toward the perikaryon. In the presence of 7 X 10(-9) M taxol neurites do grow, although they are broader and less branched than normally. The neurites of these cells appear to have normal structure except for a large number of microtubules. Taxol probably stimulates microtubule polymerization in these cultured neurons. At high levels of the drug, this action inhibits neurite initiation and outgrowth by removing free tubulin from the cytoplasm and destroying the normal control of microtubule assembly in growing neurites. The rapid inhibition suggests that microtubule assembly may occur at neurite tips. At lower concentrations, taxol may slightly enhance the mechanisms of microtubule assembly in neurons, and this alteration of normal processes changes the morphogenetic properties of the growing neurites.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Antin P. B., Forry-Schaudies S., Friedman T. M., Tapscott S. J., Holtzer H. Taxol induces postmitotic myoblasts to assemble interdigitating microtubule-myosin arrays that exclude actin filaments. J Cell Biol. 1981 Aug;90(2):300–308. doi: 10.1083/jcb.90.2.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bajer A. S., Cypher C., Molè-Bajer J., Howard H. M. Taxol-induced anaphase reversal: evidence that elongating microtubules can exert a pushing force in living cells. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6569–6573. doi: 10.1073/pnas.79.21.6569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bray D. Mechanical tension produced by nerve cells in tissue culture. J Cell Sci. 1979 Jun;37:391–410. doi: 10.1242/jcs.37.1.391. [DOI] [PubMed] [Google Scholar]
  4. Bray D., Thomas C., Shaw G. Growth cone formation in cultures of sensory neurons. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5226–5229. doi: 10.1073/pnas.75.10.5226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burnside B. Microtubules and microfilaments in newt neuralation. Dev Biol. 1971 Nov;26(3):416–441. doi: 10.1016/0012-1606(71)90073-x. [DOI] [PubMed] [Google Scholar]
  6. Daniels M. P. Fine structural changes in neurons and nerve fibers associated with colchicine inhibition of nerve fiber formation in vitro. J Cell Biol. 1973 Aug;58(2):463–470. doi: 10.1083/jcb.58.2.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daniels M. The role of microtubules in the growth and stabilization of nerve fibers. Ann N Y Acad Sci. 1975 Jun 30;253:535–544. doi: 10.1111/j.1749-6632.1975.tb19227.x. [DOI] [PubMed] [Google Scholar]
  8. De Brabander M., Geuens G., Nuydens R., Willebrords R., De Mey J. Taxol induces the assembly of free microtubules in living cells and blocks the organizing capacity of the centrosomes and kinetochores. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5608–5612. doi: 10.1073/pnas.78.9.5608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dentler W. L., Granett S., Rosenbaum J. L. Ultrastructural localization of the high molecular weight proteins associated with in vitro-assembled brain microtubules. J Cell Biol. 1975 Apr;65(1):237–241. doi: 10.1083/jcb.65.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Heidemann S. R., Landers J. M., Hamborg M. A. Polarity orientation of axonal microtubules. J Cell Biol. 1981 Dec;91(3 Pt 1):661–665. doi: 10.1083/jcb.91.3.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Kirschner M. W. Implications of treadmilling for the stability and polarity of actin and tubulin polymers in vivo. J Cell Biol. 1980 Jul;86(1):330–334. doi: 10.1083/jcb.86.1.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lasek R. J. Translocation of the neuronal cytoskeleton and axonal locomotion. Philos Trans R Soc Lond B Biol Sci. 1982 Nov 4;299(1095):313–327. doi: 10.1098/rstb.1982.0135. [DOI] [PubMed] [Google Scholar]
  15. Leterrier J. F., Liem R. K., Shelanski M. L. Interactions between neurofilaments and microtubule-associated proteins: a possible mechanism for intraorganellar bridging. J Cell Biol. 1982 Dec;95(3):982–986. doi: 10.1083/jcb.95.3.982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Letourneau P. C. Analysis of microtubule number and length in cytoskeletons of cultured chick sensory neurons. J Neurosci. 1982 Jun;2(6):806–814. doi: 10.1523/JNEUROSCI.02-06-00806.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Letourneau P. C. Cell-substratum adhesion of neurite growth cones, and its role in neurite elongation. Exp Cell Res. 1979 Nov;124(1):127–138. doi: 10.1016/0014-4827(79)90263-5. [DOI] [PubMed] [Google Scholar]
  18. Letourneau P. C. Differences in the organization of actin in the growth cones compared with the neurites of cultured neurons from chick embryos. J Cell Biol. 1983 Oct;97(4):963–973. doi: 10.1083/jcb.97.4.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Letourneau P. C. Immunocytochemical evidence for colocalization in neurite growth cones of actin and myosin and their relationship to cell--substratum adhesions. Dev Biol. 1981 Jul 15;85(1):113–122. doi: 10.1016/0012-1606(81)90240-2. [DOI] [PubMed] [Google Scholar]
  20. Letourneau P. C. Possible roles for cell-to-substratum adhesion in neuronal morphogenesis. Dev Biol. 1975 May;44(1):77–91. doi: 10.1016/0012-1606(75)90378-4. [DOI] [PubMed] [Google Scholar]
  21. Malech H. L., Root R. K., Gallin J. I. Structural analysis of human neutrophil migration. Centriole, microtubule, and microfilament orientation and function during chemotaxis. J Cell Biol. 1977 Dec;75(3):666–693. doi: 10.1083/jcb.75.3.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Manfredi J. J., Parness J., Horwitz S. B. Taxol binds to cellular microtubules. J Cell Biol. 1982 Sep;94(3):688–696. doi: 10.1083/jcb.94.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Margolis R. L., Wilson L. Microtubule treadmills--possible molecular machinery. Nature. 1981 Oct 29;293(5835):705–711. doi: 10.1038/293705a0. [DOI] [PubMed] [Google Scholar]
  24. Masurovsky E. B., Peterson E. R., Crain S. M., Horwitz S. B. Microtubule arrays in taxol-treated mouse dorsal root ganglion-spinal cord cultures. Brain Res. 1981 Aug 3;217(2):392–398. doi: 10.1016/0006-8993(81)90017-2. [DOI] [PubMed] [Google Scholar]
  25. Molè-Bajer J., Bajer A. S. Action of taxol on mitosis: modification of microtubule arrangements and function of the mitotic spindle in Haemanthus endosperm. J Cell Biol. 1983 Feb;96(2):527–540. doi: 10.1083/jcb.96.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Parness J., Horwitz S. B. Taxol binds to polymerized tubulin in vitro. J Cell Biol. 1981 Nov;91(2 Pt 1):479–487. doi: 10.1083/jcb.91.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schatten G., Schatten H., Bestor T. H., Balczon R. Taxol inhibits the nuclear movements during fertilization and induces asters in unfertilized sea urchin eggs. J Cell Biol. 1982 Aug;94(2):455–465. doi: 10.1083/jcb.94.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schiff P. B., Fant J., Horwitz S. B. Promotion of microtubule assembly in vitro by taxol. Nature. 1979 Feb 22;277(5698):665–667. doi: 10.1038/277665a0. [DOI] [PubMed] [Google Scholar]
  29. Schiff P. B., Horwitz S. B. Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1561–1565. doi: 10.1073/pnas.77.3.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schliwa M., van Blerkom J. Structural interaction of cytoskeletal components. J Cell Biol. 1981 Jul;90(1):222–235. doi: 10.1083/jcb.90.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spiegelman B. M., Lopata M. A., Kirschner M. W. Aggregation of microtubule initiation sites preceding neurite outgrowth in mouse neuroblastoma cells. Cell. 1979 Feb;16(2):253–263. doi: 10.1016/0092-8674(79)90003-5. [DOI] [PubMed] [Google Scholar]
  32. Tokunaka S., Friedman T. M., Toyama Y., Pacifici M., Holtzer H. Taxol induces microtubule-rough endoplasmic reticulum complexes and microtubule-bundles in cultured chondroblasts. Differentiation. 1983;24(1):39–47. doi: 10.1111/j.1432-0436.1983.tb01300.x. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Wehland J., Henkart M., Klausner R., Sandoval I. V. Role of microtubules in the distribution of the Golgi apparatus: effect of taxol and microinjected anti-alpha-tubulin antibodies. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4286–4290. doi: 10.1073/pnas.80.14.4286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wessells N. K., Johnson S. R., Nuttall R. P. Axon initiation and growth cone regeneration in cultured motor neurons. Exp Cell Res. 1978 Dec;117(2):335–345. doi: 10.1016/0014-4827(78)90147-7. [DOI] [PubMed] [Google Scholar]
  36. Wessells N. K., Nuttall R. P. Normal branching, induced branching, and steering of cultured parasympathetic motor neurons. Exp Cell Res. 1978 Aug;115(1):111–122. doi: 10.1016/0014-4827(78)90408-1. [DOI] [PubMed] [Google Scholar]
  37. Wood J. N., Anderton B. H. Monoclonal antibodies to mammalian neurofilaments. Biosci Rep. 1981 Mar;1(3):263–268. doi: 10.1007/BF01114913. [DOI] [PubMed] [Google Scholar]
  38. Yamada K. M., Spooner B. S., Wessells N. K. Ultrastructure and function of growth cones and axons of cultured nerve cells. J Cell Biol. 1971 Jun;49(3):614–635. doi: 10.1083/jcb.49.3.614. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES