The Cell-to-Cell Membrane Channel

Its Regulation by Cellular Phosphorylation
  • Werner R. Loewenstein
Part of the Series of the Centro de Estudios Científicos de Santiago book series (SCEC)


I shall deal with a channel that spans two cell membranes. This channel was a solution to an ancient evolutionary problem: how to interconnect the cyberneting loops of information of different cells and to do so without mixing the information sources. The seeds for this problem were sown by evolution herself as she grew, during the first one and a half billion years: a hydrophobic membrane for the cells, a barrier to keep the hard-won informational molecules from drifting apart and to keep nonsense molecules from drifting in. The barrier was instrumental in the selection of cybernetically apt units in an aqueous environment and was absolutely necessary for Darwinian evolution of cells. But, over the next two billion years, the organismic times, it became an obstacle to multicellular organization. The problem was then how to get signal molecules across the hydrophobic barrier to interconnect the units without abolishing its primitive insulating function.


Cell Junction Rous Sarcoma Virus Nonpermissive Temperature Junctional Membrane Protein Kinase Type 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Azarnia, R., and Loewenstein, W. R., 1984a, Intercellular communication and the control of growth. X. Alteration of junctional permeability by the src gene. A study with temperature-sensitive mutant Rous sarcoma virus, J. Membr. Biol. 82:191–205.PubMedCrossRefGoogle Scholar
  2. Azarnia, R., and Loewenstein, W. R., 1984b, Intercellular communication and the control of growth. XL Alteration of junctional permeability by the src gene in a revertant cell with normal cytoskeleton, J. Membr. Biol. 82:207–212.PubMedCrossRefGoogle Scholar
  3. Azarnia, R., and Loewenstein, W. R., 1984c, Intercellular communication and the control of growth. XII. Alteration of junctional permeability by simian virus 40, J. Membr. Biol. 82:213–222.PubMedCrossRefGoogle Scholar
  4. Azarnia, R., Dahl, G., and Loewenstein, W. R., 1981, Cell junction and cyclic AMP. III. Promotion of junctional membrane permeability and junctional membrane particles in a junction-deficient cell type, J. Membr. Biol. 63:133–146.PubMedCrossRefGoogle Scholar
  5. Bishop, J. M., 1982, Retroviruses and cancer genes, Adv. Cancer Res. 37:1–37.PubMedCrossRefGoogle Scholar
  6. Browne, C. L., and Wiley, H. S., 1979, Oocyte-follicle cell gap junctions in Xenopus laevis and the effects of gonadotropin on their permeability, Science 203:182–183.PubMedCrossRefGoogle Scholar
  7. Chen, W.-T., and Singer, S. J., 1982, Immunoelectron microscopic studies of the sites of cell-substratum and cell-cell contacts in cultured fibroblasts, J. Cell Biol. 95:205–222.PubMedCrossRefGoogle Scholar
  8. Collett, M. S., Purchio, A. F., and Erikson, R. L., 1980, Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine, Nature 285:167–169.PubMedCrossRefGoogle Scholar
  9. Flagg-Newton, J. L., 1979, Cyclic AMP increases junctional permeability in cultured mammalian cells, Biophys. J. 25(2):297a.Google Scholar
  10. Flagg-Newton, J. L., and Loewenstein, W. R., 1981, Cell junction and cyclic AMP. II. Modulation of junctional membrane permeability, dependent on serum and cell density, J. Membr. Biol. 63:123–131.PubMedCrossRefGoogle Scholar
  11. Flagg-Newton, J. L., Dahl, G., and Loewenstein, W. R., 1981, Cell junction and cyclic AMP. I. Upregulation of junctional membrane permeability and junctional membrane particles by administration of cyclic nucleotide or phosphodiesterase inhibitor, J. Membr. Biol. 63:105–121.PubMedCrossRefGoogle Scholar
  12. Frisque, R. J., Rifkin, D. B., and Topp, W. C., 1980, Requirement for the large T and small t proteins of SV40 in the maintenance of the transformed state, Cold Spring Harbor Symp. Quant. Biol. 44:325–331.PubMedCrossRefGoogle Scholar
  13. Gottesman, M. M., Singh, T., LeCam, A., Roth, C., Nicolas, J.-C., Cabial, F., and Pastan, I., 1981, Cyclic-AMP-dependent phosphorylation in cultured fibroblasts: A genetic approach, Cold Spring Harbor Conf. Cell Prolif. 8A: 195–209.Google Scholar
  14. Hunter, T., 1980, Proteins phosphorylated by the RSV transforming function, Cell 22:647–648.PubMedCrossRefGoogle Scholar
  15. Ito, S., Sato, E., and Loewenstein, W. R., 1974, Studies on the formation of a permeable membrane junction. II. Evolving junctional conductance and junctional insulation, J. Membr. Biol. 19:339–355.PubMedCrossRefGoogle Scholar
  16. Johnson, K. R., and Johnson, R., 1982, Bovine lens MP26 is phosphorylated in vitro by an endogenous cAMP-dependent protein kinase, Fed. Proc. 41:755.Google Scholar
  17. Johnson, R., Hammer, M., Sheridan, J., and Revel, J. P., 1974, Gap junction formation between reaggregated Novikoff hepatoma cells, Proc. Natl. Acad. Sci. U.S.A. 71:4536–4543.PubMedCrossRefGoogle Scholar
  18. Kerrick, W. G. L., and Krasner, B., 1975, Disruption of the sarcolemma of mammalian skeletal muscle fibers by homogenization, J. Appl. Physiol. 39:1052–1055.PubMedGoogle Scholar
  19. Krebs, E. G., 1972, Protein kinases, Curr. Top. Cell. Regul. 5:99–133.PubMedGoogle Scholar
  20. Kuo, J. F., and Greengard, P., 1969, Cyclic nucleotide-dependent protein kinases, IV. Widespread occurrence of adenosine 3′,5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom, Proc. Natl. Acad. Sci. U.S.A. 64:1349–1355.PubMedCrossRefGoogle Scholar
  21. Lai, C.-J., and Nathans, D., 1975, A map of temperature-sensitive mutants of simian virus 40, Virology 66:70–81.PubMedCrossRefGoogle Scholar
  22. Lau, A. F., Krzyzek, R. A., Brugge, J. S., Erikson, R. L., Schollmeyer, J., and Faras, A. J., 1979, Morphological revertants of an avian sarcoma virus-transformed mammalian cell line exhibit tumorigenicity and contain pp60src, Proc. Natl. Acad. Sci. U.S.A. 76:3904–3908.PubMedCrossRefGoogle Scholar
  23. Loewenstein, W. R., 1966, Permeability of membrane junctions, Ann. N.Y. Acad. Sci. 137:441–472.PubMedCrossRefGoogle Scholar
  24. Loewenstein, W. R., 1974, Cellular communication by permeable junctions, in Cell Membranes: Biochemistry, Cell Biology and Pathology (G. Weissmann and R. Claiborne, eds.), H.P. Publishing, New York, pp. 105–114.Google Scholar
  25. Loewenstein, W. R., 1981, Junctional intercellular communication. The cell-to-cell membrane channel, Physiol. Rev. 61:829–913.PubMedGoogle Scholar
  26. Loewenstein, W. R., Kanno, Y., and Socolar, S. J., 1978, Quantum jumps of conductance during formation of membrane channels at cell-cell junction, Nature 274:133–136.PubMedCrossRefGoogle Scholar
  27. Nawrocki, J. F., Lau, A. F., and Faras, A. J., 1984, Correlation between phosphorylation of a 34,000-molecular weight protein, pp60src-associated kinase activity, and tumorigenicity in transformed and revertant vole cells, Mol. Cell Biol. 4:212–215.PubMedGoogle Scholar
  28. Nigg, E. A., Sefton, B. M., Hunter, T., Walter, G., and Singer, S. J., 1982, Immunoflu-orescent localization of the transforming protein of Rous sarcoma virus with antibodies against a synthetic src peptide, Proc. Natl. Acad. Sci. U.S.A. 79:5322–5326.PubMedCrossRefGoogle Scholar
  29. Oliveira-Castro, G. M., and Loewenstein, W. R., 1971, Junctional membrane permeability: Effects of divalent cations, J. Membr. Biol. 5:51–77.CrossRefGoogle Scholar
  30. Radke, K., and Martin, G. S., 1979, Transformation by Rous sarcoma virus: Effects of src-gene expression on the synthesis and phosphorylation of cellular polypeptides, Cold Spring Harbor Symp. Quant. Biol. 44:975–982.CrossRefGoogle Scholar
  31. Radu, A., Dahl, G., and Loewenstein, W. R., 1982, Hormonal regulation of cell junction permeability: Upregulation by catecholamine and prostaglandin E1, J. Membr. Biol. 70:239–251.PubMedCrossRefGoogle Scholar
  32. Rose, B., and Loewenstein, W. R., 1976, Permeability of a cell junction and the local cytoplasmic free ionized calcium concentration. A study with aequorin, J. Membr. Biol. 28:87–119.PubMedCrossRefGoogle Scholar
  33. Rosen, O. M., and Krebs, E. G. (eds.), 1981, Protein Phosphorylation. Cold Spring Harbor Conference on Cell Proliferation, Vol. 8A,B, Cold Spring Harbor Laboratory, New York.Google Scholar
  34. Schriver, K., and Rohrschneider, L., 1981, Organization of pp60src and selected cytoskeletal proteins within adhesion plaques and junctions of Rous sarcoma virus-transformed cells, J. Cell Biol. 89:525–535.CrossRefGoogle Scholar
  35. Sefton, B. M., Hunter, T., Ball, E. H., and Singer, S. J., 1981, Vinculin: A cytoskeletal target of the transforming protein of Rous sarcoma virus, Cell 24:165–174.PubMedCrossRefGoogle Scholar
  36. Sompayrac, L., and Danna, K. J., 1983, A simian virus 40 dl884JtsA58 double mutant is temperature sensitive for abortative transformation, J. Virol. 46:620–625.PubMedGoogle Scholar
  37. Tevethia, S. S., Greenfield, R. S., Flyer, D. C., and Tevethia, M. J., 1980, SV-40 transplantation antigen: Relationship to SV-40 specific proteins. Cold Spring Harbor Symp. Quant. Biol. 44:235–242.PubMedCrossRefGoogle Scholar
  38. Tooze, J. (ed.), 1981, DNA Tumor Viruses: Molecular Biology of Tumor Viruses, Part 2, 2nd edition, Cold Spring Harbor Laboratory, New York.Google Scholar
  39. Unwin, P. N. T., and Ennis, P. D., 1983, Calcium-mediated changes in gap junction structure: Evidence from the low angle X-ray pattern, J. Cell Biol. 97:1459–1466.PubMedCrossRefGoogle Scholar
  40. Unwin, P. N. T., and Zampighi, G., 1980, Structure of the junction between communicating cells, Nature 283:545–549.PubMedCrossRefGoogle Scholar
  41. Wiener, E. C., and Loewenstein, W. R., 1983, Correction of cell-cell communication defect by introduction of a protein kinase into mutant cells, Nature 305:433–435.PubMedCrossRefGoogle Scholar
  42. Willingham, M. C., Jay, G., and Pastan, I., 1979, Localization of the ASV src gene product to the plasma membrane of transformed cells by electron microscopic immunocyto-chemistry, Cell 18:125–134.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Werner R. Loewenstein
    • 1
  1. 1.Department of Physiology and Biophysics, School of MedicineUniversity of MiamiMiamiUSA

Personalised recommendations