Advertisement

A Proposal to Study the Differentiation and Physiology of a Neuroblastoma: A Successful Research Grant Application Submitted to the National Institutes of Health

  • David R. Schubert
Part of the Nonprofit Management and Finance book series (NOMA)

Abstract

The differentiation and physiology of nervous tissue will be studied in vitro using cloned tissue culture lines of a mouse neuroblastoma as a model system. The parameters of the differentiation process will be defined with emphasis on control mechanisms and the induction of specific cytoplasmic and membrane proteins. Mutants which are blocked at the various steps in the differentiation process will be isolated. Similarly, the molecular biology of the cholinergic receptor and catecholamine uptake, storage, and release will be defined by studying the wild-type functions in relation to a series of mutants blocked in these functions. Finally, the nature of synaptic specificity will be studied with respect to membrane structure in electrical and, perhaps, chemical synapses in the neuroblastoma and other cloned tissue culture lines.

Keywords

Tight Junction Acetylcholine Receptor Synaptic Vesicle Transmitter Release Mouse Neuroblastoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adelman, M. R., Borisy, G. G., Shelanski, M. L., Weisenberg, R. C., and Taylor, E. W. 1968. Cytoplasmic filaments and tubules. Federation Proceedings 27:1186–1193.Google Scholar
  2. Agusti-Tocco, G., and Sato, G. 1969. Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proceedings of the National Academy of Sciences 64:311–315.CrossRefGoogle Scholar
  3. Baldessarini, R. J., and Kopin, I. J. 1966. Tritiated norepinephrine: release from brain slices by electrical stimulation. Science 152:1630–1631.CrossRefGoogle Scholar
  4. *Baxter, J. D., Harris, A. W., Tomkins, G. M., and Cohn, M. 1971. Glucocorticoid receptors in lymphoma cells in culture. Science 171:189–192.CrossRefGoogle Scholar
  5. Benedetti, E. L., and Emmelot, P. 1968. Hexagonal array of subunits in tight junctions separated from isolated rat liver plasma membranes. Journal of Cell Biology 38:15–24.CrossRefGoogle Scholar
  6. Bennett, M. V., Nokajima, Y., and Pappas, G. D. 1967. Physiology and ultrastructure of electronic junctions. Journal of Neurophysiology 30:161–179.Google Scholar
  7. Bischoff, R., and Holtzer, H. 1970. Inhibition of myoblast fusion after one round of DNA synthesis in 5-bromodeoxyuridine. Journal of Cell Biology 44:134–150.CrossRefGoogle Scholar
  8. Brightman, M. W., and Reese, T. S. 1969. Junction between intimately apposed cell membranes in the vertebrate brain. Journal of Cell Biology 40:648–677.CrossRefGoogle Scholar
  9. Butcher, R. W., Robinson, G. A., and Sutherland, E. W. 1970. The role of cyclic AMP in certain biological control systems. Pages 64–67. In G. E. W. Wolstenholme and J. Knight (editors), Control processes in multicellular organisms. J. A. Churchill, London.Google Scholar
  10. Changeux, J. P., Leuzinger, W., and Huchet, M. 1968. Specific binding of acetylcholine to acetylcholinesterase in the presence of eserine. FEBS Letters (Federation of European Biomedical Societies) 2:77–80.CrossRefGoogle Scholar
  11. Changeux, J. P., Podleski, T. R., and Wofsy, L. 1967. Affinity labeling of the acetylcholine-receptor. Proceedings of the National Academy of Sciences 58:2063–2070.CrossRefGoogle Scholar
  12. Cohn, M. 1967. Natural history of the myeloma. Cold Spring Harbor Symposia on Quantitative Biology 32:211–221.CrossRefGoogle Scholar
  13. Cohn, M. 1970. Anticipatory mechanisms of individuals. Pages 255–297. In G. E. W. Wolstenholme and J. Knight (editors), Control processes in multicellular organisms. J. A. Churchill, London.Google Scholar
  14. Cook, A. C., and Koshland, D. E. 1969. Specificity in the assembly of multisubunit proteins. Proceedings of the National Academy of Sciences 64:247–254.CrossRefGoogle Scholar
  15. Dulbecco, R. 1969. Cell transformation of viruses. Science 166:962–968.CrossRefGoogle Scholar
  16. Edds, M. V. 1967. Neuronal specificity in neuronogenesis. Pages 230–240. In G. C. Quarton, T. Melnechuk, and F. O. Schmitt (editors), The neurosciences: a study program. The Rockefeller University Press, New York.Google Scholar
  17. Goldberg, A. L., and Singer, J. J. 1969. Evidence for a role of cyclic AMP in neuromuscular transmission. Proceedings of the National Academy of Sciences 64:134–141.CrossRefGoogle Scholar
  18. *Harris, A. J., and Dennis, M. 1970. Acetylcholine sensitivity and distribution on mouse neuroblastoma cells. Science 167: 1253–1255.CrossRefGoogle Scholar
  19. Harris, H., and Watkins, J. F. 1965. Hybrid cells derived from mouse and man: artificial heterokaryons of mammalian cells from different species. Nature 205:640–646.CrossRefGoogle Scholar
  20. Heidelberger, C. 1964. Studies on the molecular mechanism of hydrocarbon carcinogenesis. Journal of Cellular and Comparative Physiology 64(Supplement I): 129–148.CrossRefGoogle Scholar
  21. *Horibata, K., and Harris, A. 1970. Mouse myelomas and lymphomas in culture. Experimental Cell Research 60:61–77.CrossRefGoogle Scholar
  22. Ivankovic, S., and Druckrey, H. 1968. Transplazentare Erzeugung maligner Tumoren des Nervensystems. I. Athyl-nitrosoharnstoff (ANH) and BD IX-Ratten. Zeitschrift für Krebsforschung und Klinische Onkologie 71:320–360.Google Scholar
  23. Iverson, L. L. 1967. The uptake and storage of noradrenaline in sympathetic nerves. Cambridge University Press, Cambridge, England, 293 pages.Google Scholar
  24. Jones, O. W., and Berg, P. 1966. Studies on the binding of RNA polymerase to polynucleotides. Journal of Molecular Biology 22:199–209.CrossRefGoogle Scholar
  25. Kreutzberg, G. W. 1969. Neuronal dynamics and axonal flow. IV. Blockage of intra-axonal enzyme transport by colchicine. Proceedings of the National Academy of Sciences 62:722–728.CrossRefGoogle Scholar
  26. Loewenstein, W. R. 1967. On the genesis of cellular communication. Developmental Biology 15:503–520.CrossRefGoogle Scholar
  27. Mannik, M. 1967. Variability in the specific interaction of H and L chains of gamma-G-globulins. Biochemistry 6:134–142.CrossRefGoogle Scholar
  28. Marantz, R., Ventilla, M., and Shelanski, M. 1969. Vinblastine-induced precipitation of microtubule protein. Science 165: 498–499.CrossRefGoogle Scholar
  29. Mueller, R. A., Thoenen, H., and Axelrod, J. 1969. Adrenal tyrosine hydroxylase: compensatory increase in activity after chemical sympathectomy. Science 163:468–469.CrossRefGoogle Scholar
  30. Nachmansohn, D. 1966. Chemical control of the permeability cycle in excitable membranes during electrical activity. Annals of the New York Academy of Sciences 137:877–900.CrossRefGoogle Scholar
  31. O’Brien, R. D., and Gimour, L. P. 1969. A musarone-binding material in electroplax and its relation to the acetylcholine receptor. I. Centrifugal assay. Proceedings of the National Academy of Sciences 63:496–503.CrossRefGoogle Scholar
  32. Politoff, A., Socolar, S. J., and Loewenstein, W. R. 1967. Metabolism and the permeability of cell membrane junctions. Biochimica et Biophysica Acta 135:791–793.CrossRefGoogle Scholar
  33. Potter, D. D., Furshpan, E. J., and Lennox, E. S. 1966. Connections between cells of the developing squid as revealed by electrophysiological methods. Proceedings of the National Academy of Sciences 55:328–336.CrossRefGoogle Scholar
  34. Riggs, A., Bourgeois, S., Newby, R., and Cohn, M. 1968. DNA binding of the Iac repressor. Journal of Molecular Biology 34:365–368CrossRefGoogle Scholar
  35. Sato, G. H., and Yasumura, Y. 1966. Retention of differentiated function in dispersed cell culture. Transactions of the New York Academy of Sciences 28:1063–1079.CrossRefGoogle Scholar
  36. Schubert, D. 1968. Immunoglobulin assembly in a mouse myeloma. Proceedings of the National Academy of Sciences 60:683–690.CrossRefGoogle Scholar
  37. *Schubert, D. 1970. Immunoglobulin biosynthesis. IV. Carbohydrate attachment to immunoglobulin subunits. Journal of Molecular Biology 51:287–301.CrossRefGoogle Scholar
  38. Schubert, D., and Cohn, M. 1968. Immunoglobulin biosynthesis. III. Blocks in defective synthesis. Journal of Molecular Biology 38:273–300.CrossRefGoogle Scholar
  39. *Schubert, D., and Cohn, M. 1970. Immunoglobin biosynthesis. V. Light chain assembly. Journal of Molecular Biology 53: 305–320.CrossRefGoogle Scholar
  40. Schubert, D., and Horibata, K. 1968. Immunoglobulin biosynthesis. II. Four independently isolated myeloma variants. Journal of Molecular Biology 38:263–273.CrossRefGoogle Scholar
  41. *Schubert, D., and Jacob, F. 1970. 5-Bromodeoxyuridine-induced differentiation of a neuroblastoma. Proceedings of the National Academy of Sciences 67:247–254.CrossRefGoogle Scholar
  42. Schubert, D., Humpreys, S., Baroni, C., and Cohn, M. 1969. In vitro differentiation of a mouse neuroblastoma. Proceedings of the National Academy of Sciences 64:316–323.CrossRefGoogle Scholar
  43. *Schubert, D., Humphreys, S., de Vitry, F., and Jacob, F. 1971. Induced differentiation of a neuroblastoma. Developmental Biology 25:514–546.CrossRefGoogle Scholar
  44. Schubert, D., Munro, A., and Ohno, S. 1968. Immunoglobin biosynthesis. I. A myeloma variant secreting light chain only. Journal of Molecular Biology 38:253–262.CrossRefGoogle Scholar
  45. Schubert, D., Roman, A., and Cohn, M. 1970. Anti-nucleic acid specificities of mouse myeloma immunoglobins. Nature 225:154–158.CrossRefGoogle Scholar
  46. Silman, I., and Karlin, A. 1969. Acetylcholine receptor: covalent attachment of depolarizing groups at the active site. Science 164:1420–1421.CrossRefGoogle Scholar
  47. Thoenen, H., and Tranzer, J. P. 1968. Möglichkeit der chemischen Sympathektomie durch selektive Zerstörung adrenerger Nervenendigugen mit 6-Hydroxydopamin (6—OH—DA). Naunyn-Schmiedebergs Archiv für Pharmakologie und Experimentelle Pathologie 261:271–288.CrossRefGoogle Scholar
  48. Thompson, E. B., Tomkins, G. M., and Curran, J. F. 1966. Induction of tyrosine alpha-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proceedings of the National Academy of Sciences 56:296–303.CrossRefGoogle Scholar
  49. Tranzer, J. P., and Thoenen, H. 1968. An electron microscopic study of selective, acute degeneration of sympathetic nerve terminals after administration of 6-hydroxydopamine. Experientia 24:155–156.CrossRefGoogle Scholar
  50. Villamil, M. F., and Kleeman, C. R. 1969. The effect of ouabain and external potassium on the ion transport of rabbit red cells. Journal of General Physiology 54:576–588.CrossRefGoogle Scholar
  51. Whittaker, V. P., and Sheridan, M. N. 1965. The morphology and acetylcholine content of isolated cerebral cortical synaptic vesicles. Journal of Neurochemistry 12:363–372.CrossRefGoogle Scholar
  52. Whittam, R. 1967. The molecular mechanism of active transport. Pages 305–312. In G. C. Quarton, T. Melnechuk, and F. O. Schmitt (editors), The neurosciences: a study program. The Rockefeller University Press, New York.Google Scholar
  53. Yaffe, D. 1968. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proceedings of the National Academy of Sciences 61:477–483.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • David R. Schubert
    • 1
  1. 1.The Salk InstituteLa JollaUSA

Personalised recommendations