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. 1975 Nov 1;67(2):461–467. doi: 10.1083/jcb.67.2.461

Microtubules and axoplasmic transport. Inhibition of transport by podophyllotoxin: an interaction with microtubule protein

J C Paulson, W O McClure
PMCID: PMC2109605  PMID: 53233

Abstract

Pharmacological evidence is presented for the involvement of microtubules in the process of fast axoplasmic transport. A quantitative measure of the inhibition of axoplasmic transport in an in vitro preparation of rat sciatic nerve is described. The alkaloids colchicine, podophyllotoxin, and vinblastine, which are known both to disrupt microtubules and to bind to the protein subunit of microtubules, are inhibitors of axoplasmic transport. Lumicolchine and picropodophyllin, unlike their respective isomers colchicine and podophyllotoxin, are poor inhibitors of axoplasmic transport. The dissociation constants for the binding of colchicine, lumicolchicine, podophyllotoxin, and picropodophyllin to purified microtubule protein from rat brain have been measured. Inhibition of axoplasmic transport by these drugs correlates favorably with their affinities of microtubule protein.

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Selected References

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  1. Anderson L. E., McClure W. O. An improved scintillation cocktail of high-solubilizing power. Anal Biochem. 1973 Jan;51(1):173–179. doi: 10.1016/0003-2697(73)90465-x. [DOI] [PubMed] [Google Scholar]
  2. Borisy G. G., Taylor E. W. The mechanism of action of colchicine. Colchicine binding to sea urchin eggs and the mitotic apparatus. J Cell Biol. 1967 Aug;34(2):535–548. doi: 10.1083/jcb.34.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bryan J. Definition of three classes of binding sites in isolated microtubule crystals. Biochemistry. 1972 Jul 4;11(14):2611–2616. doi: 10.1021/bi00764a010. [DOI] [PubMed] [Google Scholar]
  4. Byers M. R. Structural correlates of rapid axonal transport: evidence that microtubules may not be directly involved. Brain Res. 1974 Jul 19;75(1):97–113. doi: 10.1016/0006-8993(74)90773-2. [DOI] [PubMed] [Google Scholar]
  5. Crooks R. F., McClure W. O. The effect of cytocholasin B on fast axoplasmic transport. Brain Res. 1972 Oct 27;45(2):643–646. doi: 10.1016/0006-8993(72)90499-4. [DOI] [PubMed] [Google Scholar]
  6. Edelman G. M., Yahara I., Wang J. L. Receptor mobility and receptor-cytoplasmic interactions in lymphocytes. Proc Natl Acad Sci U S A. 1973 May;70(5):1442–1446. doi: 10.1073/pnas.70.5.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Edstrom A., Mattsson H. Fast axonal transport in vitro in the sciatic system of the frog. J Neurochem. 1972 Jan;19(1):205–221. doi: 10.1111/j.1471-4159.1972.tb01270.x. [DOI] [PubMed] [Google Scholar]
  8. Gabbay K. H., Tze W. J. Inhibition of glucose-induced release of insulin by aldose reductase inhibitors. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1435–1439. doi: 10.1073/pnas.69.6.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kingsbury E. W., Voelz H. Induction of helical arrays of ribosomes by vinblastine sulfate in Escherichia coli. Science. 1969 Nov 7;166(3906):768–769. doi: 10.1126/science.166.3906.768. [DOI] [PubMed] [Google Scholar]
  10. Mizel S. B., Wilson L. Nucleoside transport in mammalian cells. Inhibition by colchicine. Biochemistry. 1972 Jul 4;11(14):2573–2578. doi: 10.1021/bi00764a003. [DOI] [PubMed] [Google Scholar]
  11. Ochs S., Smith C. B. Fast axoplasmic transport in mammalian nerve in vitro after block of glycolysis with iodoacetic acid. J Neurochem. 1971 Jun;18(6):833–843. doi: 10.1111/j.1471-4159.1971.tb12013.x. [DOI] [PubMed] [Google Scholar]
  12. Oliver J. M., Ukena T. E., Berlin R. D. Effects of phagocytosis and colchicine on the distribution of lectin-binding sites on cell surfaces. Proc Natl Acad Sci U S A. 1974 Feb;71(2):394–398. doi: 10.1073/pnas.71.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Owellen R. J., Owens A. H., Jr, Donigian D. W. The binding of vincristine, vinblastine and colchicine to tubulin. Biochem Biophys Res Commun. 1972 May 26;47(4):685–691. doi: 10.1016/0006-291x(72)90546-3. [DOI] [PubMed] [Google Scholar]
  14. Paulson J. C., McClure W. O. Microtubules and axoplasmic transport. Brain Res. 1974 Jun 20;73(2):333–337. doi: 10.1016/0006-8993(74)91053-1. [DOI] [PubMed] [Google Scholar]
  15. Paulson J. C., McClure W. O. The lack of correlation between hallucinogenesis and inhibition of axoplasmic transport. Mol Pharmacol. 1974 May;10(3):419–424. [PubMed] [Google Scholar]
  16. Smith D. S., Järlfors U., Beránek R. The organization of synaptic axcplasm in the lamprey (petromyzon marinus) central nervous system. J Cell Biol. 1970 Aug;46(2):199–219. doi: 10.1083/jcb.46.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. TAYLOR E. W. THE MECHANISM OF COLCHICINE INHIBITION OF MITOSIS. I. KINETICS OF INHIBITION AND THE BINDING OF H3-COLCHICINE. J Cell Biol. 1965 Apr;25:SUPPL–SUPPL:160. doi: 10.1083/jcb.25.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Taylor A., Mamelak M., Reaven E., Maffly R. Vasopressin: possible role of microtubules and microfilaments in its action. Science. 1973 Jul 27;181(4097):347–350. doi: 10.1126/science.181.4097.347. [DOI] [PubMed] [Google Scholar]
  19. Trifaró J. M., Collier B., Lastowecka A., Stern D. Inhibition by colchicine and by vinblastine of acetylcholine-induced catecholamine release from the adrenal gland: an anticholinergic action, not an effect upon microtubules. Mol Pharmacol. 1972 Mar;8(2):264–267. [PubMed] [Google Scholar]
  20. Wilson L., Bryan J., Ruby A., Mazia D. Precipitation of proteins by vinblastine and calcium ions. Proc Natl Acad Sci U S A. 1970 Jul;66(3):807–814. doi: 10.1073/pnas.66.3.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wilson L., Friedkin M. The biochemical events of mitosis. I. Synthesis and properties of colchicine labeled with tritium in its acetyl moiety. Biochemistry. 1966 Jul;5(7):2463–2468. doi: 10.1021/bi00871a042. [DOI] [PubMed] [Google Scholar]
  22. Wilson L., Friedkin M. The biochemical events of mitosis. II. The in vivo and in vitro binding of colchicine in grasshopper embryos and its possible relation to inhibition of mitosis. Biochemistry. 1967 Oct;6(10):3126–3135. doi: 10.1021/bi00862a021. [DOI] [PubMed] [Google Scholar]
  23. Wilson L. Properties of colchicine binding protein from chick embryo brain. Interactions with vinca alkaloids and podophyllotoxin. Biochemistry. 1970 Dec 8;9(25):4999–5007. doi: 10.1021/bi00827a026. [DOI] [PubMed] [Google Scholar]
  24. Wisniewski H., Shelanski M. L., Terry R. D. Effects of mitotic spindle inhibitors on neurotubules and neurofilaments in anterior horn cells. J Cell Biol. 1968 Jul;38(1):224–229. doi: 10.1083/jcb.38.1.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wunderlich F., Müller R., Speth V. Direct evidence for a colchicine-induced impairment in the mobility of membrane components. Science. 1973 Dec 14;182(4117):1136–1138. doi: 10.1126/science.182.4117.1136. [DOI] [PubMed] [Google Scholar]

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