Cell-to-Cell Communication

Permeability, Formation, Genetics, and Functions of the Cell-Cell Membrane Channel
  • Werner R. Loewenstein


In formulating Cell Theory, Schleiden(1) wrote in 1838: “Every higher organism is an aggregate of fully circumscribed and self-contained unit beings, the cells.” This basic tenet has been extraordinarily fruitful and influential in biology and medicine, and in many aspects its usefulness continues unabated. However, since the mid-1960s it has become clear that cellular circumscription is generally not complete; a wide variety of cells turned out to be interconnected by membrane channels at their junction.(2,3) Small molecules pass freely from one cell interior to another through these junctional channels so that the connected cell ensemble, rather than the single cell, is the unit in many cellular functions; there is cell autonomy only in respect to the larger molecules that do not permeate the junctional channels.


Intercellular Communication Electrical Coupling Membrane Channel Membrane Biology Channel Permeability 
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  1. 1.
    Schleiden, M. J. 1838. Beiträge zur Phytogenesis. Müllers Arch. Anat. Physiol. Wiss. Med. 1838: 137–176.Google Scholar
  2. 2.
    Loewenstein, W. R. 1966. Permeability of membrane junctions. Ann. N.Y. Acad. Sci. 137: 441–472.PubMedCrossRefGoogle Scholar
  3. 3.
    Loewenstein, W. R. 1975. Permeable junctions. Cold Spring Harbor Symp. Quant. Biol 40: 49–63.CrossRefGoogle Scholar
  4. 4.
    Furshpan, E. J., and D. D. Potter. 1968. Low resistance junctions between cells in embryos and tissue culture. Curr. Top. Dey. Biol. 3: 95–116.CrossRefGoogle Scholar
  5. 5.
    Singer, S. J., and G. L. Nicolson. 1972. The fluid mosaic model of the structure of cell membranes. Science 17: 720–729.CrossRefGoogle Scholar
  6. 6.
    Loewenstein, W. R. 1974. Cellular communication by permeable junctions. In: Cell Membranes: Biochemistry, Cell Biology and Pathology. G. Weissman and R. Claiborne, eds. H. P. Publ. Co., New York. pp. 105–114.Google Scholar
  7. 7.
    Goodenough, D. A., and J. P. Revel. 1970. A fine structural analysis of intercellular junctions in the mouse liver. J. Cell Biol. 45: 272–288.PubMedCrossRefGoogle Scholar
  8. 8.
    McNutt, N. S., and R. S. Weinstein. 1973. Membrane ultrastructure and mammalian intercellular junction. Prog. Biophys. Mol. Biol. 26: 45–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Goodenough, D. A. 1975. The structure and permeability of isolated hepatocyte gap junctions. Cold Spring Harbor Symp. Quant. Biol. 40: 37–45.CrossRefGoogle Scholar
  10. 10.
    Peracchia, C., and M. E. Fernandez-Jaimovich. 1975. Isolation of intramembranous particles from gap junction. J. Cell Biol. 67: 330a.Google Scholar
  11. 11.
    Gilula, N. B., and M. L. Epstein. 1976. Cell-to-cell communication, gap junction and calcium. Symp. Soc. Exp. Biol. 30: 257–272.Google Scholar
  12. 12.
    Ito, S., E. Sato, and W. R. Loewenstein. 1974. Studies on the formation of a permeable cell membrane junction. II. Evolving junctional conductance and junctional insulation. J. Membr. Biol. 19: 339–355.PubMedCrossRefGoogle Scholar
  13. 13.
    Loewenstein, W. R., and Y. Kanno. 1964. Studies on an epithelial (gland) cell junction. I. Modifications of surface membrane permeability. J. Cell Biol. 22: 565–586.Google Scholar
  14. 14.
    Pappas, G. D., and M. V. L. Bennett. 1966. Specialized junctions involved in electrical transmission between neurons. Ann. N.Y. Acad. Sci. 137: 495–511.PubMedCrossRefGoogle Scholar
  15. 15.
    Rose, B. 1971. Intercellular communication and some structural aspects of cell junctions in a simple cell system. J. Membr. Biol. 5: 1–19.CrossRefGoogle Scholar
  16. 16.
    Sheridan, J. 1971. Dye movement and low resistance junctions between reaggregated embryonic cells. Del,. Biol. 26: 627–643.Google Scholar
  17. 17.
    Azarnia, R., and W. R. Loewenstein. 1971. Intercellular communication and tissue growth. V. A cancer cell strain that fails to make permeable membrane junctions with normal cells. J. Membr. Biol. 6: 368–385.CrossRefGoogle Scholar
  18. 18.
    Azarnia, R., W. Michalke, and W. R. Loewenstein. 1972. Intercellular communication and tissue growth. VI. Failure of exchange of endogenous molecules between cancer cells with defective junctions and noncancerous cells. J. Membr. Biol. 10: 247–258.PubMedCrossRefGoogle Scholar
  19. 19.
    Pollack, G. H. 1976. Intercellular coupling in the atrioventricular node and other tissues of the rabbit heart. J. Physiol. (Land.) 255: 275–298.Google Scholar
  20. 20.
    Kanno, Y., and W. R. Loewenstein. 1966. Cell-to-cell passage of large molecules. Nature 212: 629–630.PubMedCrossRefGoogle Scholar
  21. 21.
    Potter, D. D., E. J. Furshpan, and E. S. Lennox. 1966. Connections between cells of the developing squid as revealed by electrophysiological methods. Proc. Natl. Acad. Sci. U.S.A. 55: 328–344.PubMedCrossRefGoogle Scholar
  22. 22.
    Payton, B. W., M. V. L. Bennett, and G. D. Pappas. 1969. Permeability and structure of junctional membranes at an electrotonic synapse. Science 166: 16411656.Google Scholar
  23. 23.
    Johnson, R., and J. D. Sheridan. 1971. Junctions between cancer cells in culture: Ultrastructure and permeability. Science 174: 717–734.PubMedCrossRefGoogle Scholar
  24. 24.
    Simpson, I., B. Rose, and W. R. Loewenstein. 1977. Size limit of molecules permeating the junctional membrane channels. Science 195: 294–296.PubMedCrossRefGoogle Scholar
  25. 25.
    Oliveira-Castro, G. M., and W. R. Loewenstein. 1971. Junctional membrane permeability: Effects of divalent cations. J. Membr. Biol. 5:51–77. Google Scholar
  26. 26.
    Rose, B., and W. R. Loewenstein. 1975. Permeability of cell junction depends on local cytoplasmic calcium activity. Nature 254: 250–252.PubMedCrossRefGoogle Scholar
  27. 27.
    Rose, B., and W. R. Loewenstein. 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
  28. 28.
    Shimomura, O., and F. H. Johnson. 1969. Properties of the bioluminescent protein aequorin. Biochemistry 8: 3991–4008.PubMedCrossRefGoogle Scholar
  29. 29.
    Rose, B., and W. R. Loewenstein. 1975. Calcium ion distribution in cytoplasm visualized by aequorin: Diffusion in the cytosol is restricted due to energized sequestering. Science 190:1204–1206.Google Scholar
  30. 30.
    Délèze, J., and W. R. Loewenstein. 1976. Permeability of a cell junction during intracellular injection of divalent cations. J. Membr. Biol. 28: 71–86.PubMedCrossRefGoogle Scholar
  31. 31.
    Rose, B., I. Simpson, W. R. Loewenstein. 1977. Calcium ion produces graded changes in permeability of membrane channels in cell junction. Nature 267: 625627.Google Scholar
  32. 32.
    Loewenstein, W. R. 1967. Cell surface membranes in close contact. Role of calcium and magnesium ions. J. Colloid Interface Sci. 25: 34–46.PubMedCrossRefGoogle Scholar
  33. 33.
    Loscalzo, J., G. H. Reed, and A. Weber. 1976. Conformational change and cooperativity in actin filaments free of tropomyosin. Proc. Natl. Acad. Sci. U.S.A. 72: 3412–3428.CrossRefGoogle Scholar
  34. 34.
    Haynes, D. 1977. Divalent cation-ligand interactions of phospholipid membranes. In: Metal-Ligand Interactions in Organic Chemistry and Biochemistry. Part II. B. Pullman and M. Goldblum, eds. Ninth Jerusalem Symp. D. Ridell, Dordrecht, Holland. pp. 189–212.Google Scholar
  35. 35.
    Peracchia, C., and A. Dulhunty. 1976. Low resistance junctions in crayfish. Structural changes with functional uncoupling. J. Cell Biol. 70: 419–439.PubMedCrossRefGoogle Scholar
  36. 36.
    Loewenstein, W. R., and R. D. Penn. 1967. Intercellular communication and tissue growth. II. Tissue regeneration. J. Cell Biol. 33: 235–242.PubMedCrossRefGoogle Scholar
  37. 37.
    Penn, R. D. 1966. Ionic communication between liver cells. J. Cell Biol. 29:171–173.Google Scholar
  38. 38.
    Loewenstein, W. R. 1968. Some reflections on growth and differentiation. Perspect. Biol. Med. 11: 260–272.PubMedGoogle Scholar
  39. 39.
    Loewenstein, W. R. 1968. Communication through cell junctions. Implications in growth control and differentiation. Dev. Biol. 19 (Suppl. 2): 151–183.Google Scholar
  40. 40.
    Slack, C., and J. P. Palmer, 1969. The permeability of intercellular junctions in the early embryo of Xenopus laevis, studies with fluorescent tracer. Exp. Cell Res. 55: 416–431.PubMedCrossRefGoogle Scholar
  41. 41.
    Warner, A. E. 1973. Electrical properties of the actoderm in the amphibian embryo during induction and early development of the nervous system. J. Physiol. (Lond.) 235: 267–286.Google Scholar
  42. 42.
    Lehninger, A. L., E. Carafoli, and C. S. Rossi. 1967. Energy-linked ion movements in mitochondrial systems. Adv. Enzymol. 29: 259–320.PubMedGoogle Scholar
  43. 43.
    Moore, L., T. Chen, H. R. Knapp, and E. J. Landon. 1975. Energy-dependent calcium sequestration activity in rat liver microsomes. J. Biol. Chem. 250: 4562–4568.PubMedGoogle Scholar
  44. 44.
    Baker, P. F., and A. C. Crawford. 1972. Mobility and transport of magnesium in squid giant axons. J. Physiol. (Lond.) 227: 855–871.Google Scholar
  45. 45.
    Loewenstein. W. R., M. Nakas, and S. J. Socolar. 1967. Junctional membrane uncoupling. Permeability transformations at a cell membrane junction. J. Gen. Physiol. 50:1865–1891.Google Scholar
  46. 46.
    Politoff, A. L., S. J. Socolar, and W. R. Loewenstein. 1969. Permeability of a cell membrane junction. Dependence on energy metabolism. J. Gen. Physiol. 53: 498515.Google Scholar
  47. 47.
    Rose, B., and W. R. Loewenstein. 1971. Junctional membrane permeability. Depression by substitution of Li for extracellular Na, and by long-term lack of Ca and Mg; restoration by cell repolarization. J. Membr. Biol. 5: 20–50.CrossRefGoogle Scholar
  48. 48.
    Délèze, J. 1970. The recovery of resting potential and input resistance in sheep heart injured by knife or laser. J. Physiol. (Lond.) 208: 547–564.Google Scholar
  49. 49.
    Délèze, J. 1975. The site of healing over after local injury in the heart. In: Recent Advances in Studies on Cardiac Structure and Metabolism, Vol. 5. A. Fleckenstein and N. S. Dhalla, eds. Univ. Park Press, Baltimore. pp. 223–235.Google Scholar
  50. 50.
    de Mello, W. C. 1975. Effect of intracellular injection of calcium and strontium on cell communication in heart. J. Physiol. (Lond.) 250: 231–245.Google Scholar
  51. 51.
    Ito, S., E. Sato, and W. R. Loewenstein. 1974. Studies on the formation of a permeable cell membrane junction. I. Coupling under various conditions of membrane contact. Colchicine, cytochalasin B, dinitrophenol. J. Membr. Biol. 19: 305–337.PubMedCrossRefGoogle Scholar
  52. 52.
    Ito, S., and W. R. Loewenstein. 1969. Ionic communication between early embryonic cells. Del). Biol. 19: 228–243.CrossRefGoogle Scholar
  53. 53.
    Johnson, R., M. Hammer, J. Sheridan, and J. P. Revel. 1974. Gap junction formation between reaggregated Novikoff hepatoma cells. Proc. Natl. Acad. Sci. U.S.A. 71: 4536–4540.PubMedCrossRefGoogle Scholar
  54. 54.
    Edidin, M. 1974. Rotational and translational diffusion in membranes. Annu. Rev. Biophys. Bioeng. 3: 179201.Google Scholar
  55. 55.
    Schlesinger, J., D. Axelrod, D. E. Koppel, W. W. Webb, and E. L. Elson. 1977. Lateral transport of a lipid probe and labeled proteins on a cell membrane. Science 195:4275–4287.Google Scholar
  56. 56.
    Azarnia, R., W. J. Larsen, and W. R. Loewenstein. 1974. The membrane junctions in communicating and non-communicating cells, their hybrids and segregants. Proc. Natl. Acad. Sci. U.S.A. 71: 880–884.PubMedCrossRefGoogle Scholar
  57. 57.
    Azarnia, R., and W. R. Loewenstein. 1977. Intercellular communication and tissue growth. VIII. A genetic analysis of junctional communication and cancerous growth. J. Membr. Biol. 34: 1–37.PubMedCrossRefGoogle Scholar
  58. 58.
    Larsen, W. J., R. Azarnia, and W. R. Loewenstein. 1977. Intercellular communication and tissue growth. IX. Junctional membrane structure of hybrids between communication-competent and communication-incompetent cells. J. Membr. Biol. 34: 39–54.PubMedCrossRefGoogle Scholar
  59. 59.
    Jamakosmanovic, A., and W. R. Loewenstein. 1968. Intercellular communication and tissue growth. III. Thyroid cancer. J. Cell Biol. 38: 556–561.PubMedCrossRefGoogle Scholar
  60. 60.
    Lewis, S. A., D. C. Eaton, and J. M. Diamond. 1976. The mechanism of Na+ transport in rabbit urinary bladder. J. Membr. Biol. 28: 41–70.PubMedCrossRefGoogle Scholar
  61. 61.
    Nagel, W. 1976. Intercellular junctions of frog skin epithelial cells. Nature 264: 469–471.PubMedCrossRefGoogle Scholar
  62. 62.
    Furshpan, E. J., and D. D. Potter. 1959. Transmission at the giant motor synapses of the crayfish. J. Physiol. (Lond.) 145:289–325.Google Scholar
  63. 63.
    Woodbury, J. W., and W. E. Crill. 1961. In: Nervous Inhibition. E. Flong, ed. Pergamon, Oxford.Google Scholar
  64. 64.
    Weidmann, S. 1952. The electrical constants of Purkinje fibers. J. Physiol. (Lond.) 118: 348–360.Google Scholar
  65. 65.
    Weidmann, S. 1966. The diffusion of radio potassium across intercalated disks of mammalian cardiac muscle. J. Physiol. (Lond.) 187: 323–342.Google Scholar
  66. 66.
    Barr, L., M. M. Dewey, and W. Berger. 1965. Propagation of the action potentials and the structure of the nexus in cardiac muscle. J. Gen. Physiol. 48: 797–823.PubMedCrossRefGoogle Scholar
  67. 67.
    Dewey, M. M., and L. Barr. 1964. A study of the structure and distribution of the nexus. J. Cell Biol. 23: 553–585.PubMedCrossRefGoogle Scholar
  68. 68.
    Ito, S., and N. Hori. 1966. Electrical characteristics of Triturus egg cells during cleavage. J. Gen. Physiol. 49:1019–1027.Google Scholar
  69. 69.
    Sheridan, J. 1968. Electrophysiological evidence for low resistance junctions in the early chick embryo. J. Cell Biol. 37: 650–659.PubMedCrossRefGoogle Scholar
  70. 70.
    Wolpert, L. 1971. Positional information and pattern formation. Curr. Top. Dev. Biol. 6: 883–224.Google Scholar
  71. 71.
    Crick, F. H. C. 1970. Diffusion in embryogenesis. Nature 225:420–422.Google Scholar
  72. 72.
    Loewenstein, W. R. 1969. Transfer of information through cell junctions and growth control. In: EighthCanadian Cancer Conference, Honey Harbour. J. F. Morgan, ed. Pergamon, Toronto. pp. 162–170.Google Scholar
  73. 73.
    Burton, A. C. 1971. Cellular communication, contact inhibition, cell clocks, and cancer. Perspect. Biol. Med. 14: 301–318.PubMedGoogle Scholar
  74. 74.
    Burton, A. C. 1975. The role of biochemical rhythms in contact inhibition of cellular division. In: Cellular Membranes and Tumor Cell Behavior. Williams & Wilkins, Baltimore. pp. 249–266.Google Scholar
  75. 75.
    Socolar, S. J. 1973. Cell coupling in epithelia. Exp. Eye Res. 15: 693–698.PubMedCrossRefGoogle Scholar
  76. 76.
    Loewenstein, W. R. 1975. Intercellular communications in normal and neoplastic tissues. In: Cellular Membranes and Tumor Cell Behavior. Williams & Wilkins, Baltimore. pp. 239–248.Google Scholar
  77. 77.
    Borek, C., S. Higashino, and W. R. Loewenstein. 1969. Intercellular communication and tissue growth. IV. Conductance of membrane junctions of normal and cancerous cells in culture. J. Membr. Biol. 1: 274–293.CrossRefGoogle Scholar
  78. 78.
    Sheridan, J. 1970. Low resistance junctions between cancer cells in various solid tumors. J. Cell Biol. 45: 91–99.PubMedCrossRefGoogle Scholar
  79. 79.
    Azamia, R., and W. R. Loewenstein. 1976. Intercellular communication and tissue growth. VII. A cancer cell strain with retarded formation of permeable membrane junction and reduced exchange of a 330-dalton molecule. J. Membr. Biol. 30:175–186.Google Scholar
  80. 80.
    Subak-Sharpe, H., R. R. Burk, and J. D. Pitts. 1969. Metabolic cooperation between biochemically marked mammalian cells in culture. J. Cell Sci. 4: 353–360.PubMedGoogle Scholar
  81. 81.
    Cox, R. P., M. R. Kraus, M. E. Balis, and J. Dancis. 1970. Evidence of transfer of enzyme product as the basis of metabolic cooperation between tissue culture fibroblasts of Lesch-Nyhan disease and normal cells. Proc. Natl. Acad. Sci. U.S.A.67:1573–1579.Google Scholar
  82. 82.
    Pitts, J. D. 1971. Growth control in cell culture. In: Ciba Foundation Symposium. G. Wolstenholme and J. Knight, eds. Churchill, Livingston, London. p. 89Google Scholar
  83. 83.
    Gilula, N. B., O. R. Reeves, and A. Steinbach. 1972. Metabolic coupling, ionic coupling and cell contacts. Nature 235:262–265.Google Scholar
  84. 84.
    Pitts, J. D. 1975. How do animal cells communicate? Nature255:371.Google Scholar
  85. 85.
    Loewenstein, W. R., and S. J. Socolar. 1978. Methods for studying cell-cell communication. In: Methods in Membrane Biology,Vol. 6. E. Korn, ed. Plenum, New York.Google Scholar
  86. 86.
    Weiss, M. C., J. Todaro, and H. Green. 1968. Properties of a hybrid between lives sensitive and insensitive to contact inhibition of cell division. J. Cell. Physiol.71:105–108.PubMedCrossRefGoogle Scholar
  87. 87.
    Klein, G., V. Bregula, F. Wiener, and H. Harris. 1971. The analysis of malignancies by cell fusion. I. Hybrids between tumor cells and L cell derivatives. J. Cell Sci.8:659–672.Google Scholar
  88. 88.
    Harris, H. 1971. Cell fusion and the analysis of malignancy. Proc. R. Soc. Lond. 179: 1–20.PubMedCrossRefGoogle Scholar
  89. 89.
    Azarnia, R., and W. R. Loewenstein. 1973. Parallel correction of cancerous growth and of a genetic defect of cell-to-cell communication. Nature 241: 445–457.CrossRefGoogle Scholar
  90. 90.
    Loewenstein, W. R. 1978. Junctional intercellular communication and growth control. B.B.A. Rev. Cancer. In press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Werner R. Loewenstein
    • 1
  1. 1.Department of Physiology and BiophysicsUniversity of Miami School of MedicineMiamiUSA

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