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Hepatocyte Gap Junctions: Metabolic Regulation and Possible Role in Liver Metabolism

  • Juan C. Sáez
  • Michael V. L. Bennett
  • David C. Spray
Part of the Series of the Centro de Estudios Científicos de Santiago book series (SCEC)

Abstract

Over the past three decades, it has become clear that cells of most tissues communicate through specialized intercellular structures called gap junctions(1) which have also been termed nexus or maculae communicantes. One of the most exhaustively studied examples of this type of intercellular communication is that between hepatocytes, which is emphasized in this chapter. In electron micrographs of thin sections, gap junctions are seen as specialized regions of contact where apposed plasma membranes of adjacent cells are separated by a gap of 2–3 nm (Fig. 1A). In electron micrographs of freeze fracture replicas, hepatocyte gap junctions show arrays or plaques of 8.5–9.5 nm intramembrane particles cleaving with the P face (Fig. 1B); complementary pits appear on the E face. In the center of the fractured particles a dimple is commonly discernible that presumably represents the central aqueous lumen of the gap junction channel. Channels of isolated gap junctions can form a regular hexagonal array, and application of Fourier transform techniques reveal substructure in which each hemichannel or con-nexon is made up of six subunits.(2) The hemichannels or connexons crossing each plasma membrane protrude into the extracellular gap, where they connect to those in the other half of the junction to form the complete aqueous channel(3) (Fig. 1C).

Keywords

Couple Cell Junctional Conductance Freeze Fracture Replica Hepatocyte Plasma Membrane Appose Plasma Membrane 
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.

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References

  1. 1.
    Bennett, M. V. L., and Spray, D. C., (Eds.), 1985, Gap Junctions, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.Google Scholar
  2. 2.
    Unwin, P. N. T., and Ennis, P. D., 1984, Two configurations of the channel-forming membrane protein, Nature (London) 307: 609–613.CrossRefGoogle Scholar
  3. 3.
    Makowski, L., Caspar, D. L. D., Phillips, W. C., and Goodenough, D. A., 1984, Gap junction structure. V. Structural chemistry inferred from x-ray diffraction measurements on sucrose accessibility and trypsin susceptibility, J. Mol. Biol. 174: 449–481.PubMedCrossRefGoogle Scholar
  4. 4.
    Hertzberg, E. L., 1984, A detergent-independent procedure for the isolation from rat liver, J. Biol. Chem. 259: 9936–9943.PubMedGoogle Scholar
  5. 5.
    Paul, D., 1986, Molecular cloning of cDNA for rat liver gap junction protein, J. Cell Biol. 103: 123–134.PubMedCrossRefGoogle Scholar
  6. 6.
    Beyer, E. C., Paul, D., and Goodenough, D. A., 1987, Connexin 43: A protein from rat heart homologous to gap junction protein from liver, J. Cell Biol. 105: 2621–2629.PubMedCrossRefGoogle Scholar
  7. 7.
    Nicholson, B. J., and Zhang, J-T., 1988, Multiple protein components in a single gap junction: Cloning of a second hepatic gap junction protein (M r 21,000), in: Modem Cell Biology, Vol. 7 (E. L. Hertzenberg and R. G. Johnson, Eds.), Alan R. Liss, New York, pp. 207–218.Google Scholar
  8. 8.
    Nicholson, B. J., Dermietzel, R., Teplow, D. B., Traub, O., Willecke, K., and Revel, J.-P., 1987, Two homologous protein components of hepatic gap junctions, Nature 329: 732–734.PubMedCrossRefGoogle Scholar
  9. 9.
    Exton, J. H., Cherington, A. D., Blackmore, P. F., Dehaye, J.-P., Strickland, W. G., Jordan, J. E., and Chisman, T. D., 1986, Hormonal regulation of liver glycogen metabolism, in: Protein Phosphorylation, Cold Spring Harbor Conferences on Cell Proliferation, Vol. 8. (O. M. Rosen and E. G. Krebs, Eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., pp. 503–528.Google Scholar
  10. 10.
    Sáez, J. C., Spray, D. C., Nairn, A. C., Hertzberg, E. L., Greengard, P., and Bennett, M. V. L., 1986, cAMP increases junctional conductance and stimulates phosphorylation of the 27 kDa principal gap junction polypeptide, Proc. Natl. Acad. Sci. USA 83: 2473–2477.Google Scholar
  11. 11.
    Sáez, J. C., Nairn, A. C., Spray, D. C., Hertzberg, E. L., Greengard, P., and Bennett, M. V. L., 1987, The major 27 kD gap junction protein is phosphorylated by cAMP dependent and Ca2+ -dependent protein kinases, Soc. Neurose. 13: 1133.Google Scholar
  12. 12.
    Yamasaki, H., and Mesnil, M., 1987, Cellular communication in cell transformation, in: Biochemical Mechanisms and Regulation of Intercellular Communication (M. A. Mehlman, Ed.), Princeton Scientific Publication Co., Inc., Princeton, N.J., pp. 181–207.Google Scholar
  13. 13.
    Enamoto, T., Martel, N., Kanno, Y, and Yamasaki, H., 1984, Inhibition of cell communication between Balb/c 3T3 cells by tumor promoters and protection by cAMP, J. Cell. Physiol. 121: 323–333.CrossRefGoogle Scholar
  14. 14.
    Sáez, J. C., Nairn, A. C., Czernick, A. J., Spray, D. C., Hertzberg, E. L., Greengard, P., and Bennett, M. V. L., 1990, Phosphorylation of connexin 32, the main hepatocyte gap junction protein, by cAMP-dependent protein kinase, protein kinase-C and Ca2+ /calmodulin-dependent protein kinase. (Submitted for publication.)Google Scholar
  15. 15.
    Yada, T., Rose, B., and Loewenstein, W. R., 1985, Diacylglycerol down regulates membrane permeability: TMB-8 blocks this effect, J. Membr. Biol. 88: 217–232.PubMedCrossRefGoogle Scholar
  16. 16.
    Sâez, J. C., Gregory, W. A., Dermietzel, R., Hertzberg, E. L., Watanabe, T., Reid, L. M., Bennett, M. V. L., and Spray, D.C., 1989, cAMP extends the functional lifespan of gap junctions in cultured rat hepatocytes, Am. J. Physiol. 257: C1-C11.PubMedGoogle Scholar
  17. 17.
    Spray, D. C., Fujita, Y., Sáez, J. C., Choi, H., Rosenberg, L. C., and Reid, L. M., 1987, Glycosaminoglycans and proteoglycans induce gap junction synthesis and function in primary liver cultures, J. Cell Biol. 105: 541–551.PubMedCrossRefGoogle Scholar
  18. 18.
    Watanabe, T., Sáez, J. C., Spray, D. C., and Reid, L. M., 1987, Heparin potentiates the regulation by hormones and growth factors of liver-specific mRNA expression in cultured hepatocytes, J. Cell Biol. 105: 356.Google Scholar
  19. 19.
    Sâez, J. C., Connor, J. A., Spray, D. C., and Bennett, M. V. L., 1989, Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-triphosphate, and to calcium ions, Proc. Natl. Acad. Sci. USA 86: 2708–2712.PubMedCrossRefGoogle Scholar
  20. 20.
    Graf, J., and Petersen, O. H., 1978, Cell membrane potential and resistance in liver, J. Physiol. 284: 105–126.PubMedGoogle Scholar
  21. 21.
    Marchmount, R. J., and Houlay, M. D., 1980, Insulin triggers cAMP-dependent activation and phosphorylation of a plasma membrane cAMP phosphodiesterase, Nature (London) 286: 904–906.CrossRefGoogle Scholar
  22. 22.
    Sâez, J. C., Bennett, M. V. L., and Spray, D. C., 1987, Carbon tetrachloride at hepatotoxic levels blocks reversibly gap junctions between rat hepatocytes, Science 236: 967–969.PubMedCrossRefGoogle Scholar
  23. 23.
    Exton, J. H., 1980, Mechanisms involved in a-adrenergic phenomena: Role of calcium ions in actions of catecholamines in liver and other tissues, Am. J. Physiol. 238: E3-E12.PubMedGoogle Scholar
  24. 24.
    Garrison, J. C., and Borland, M. K., 1979, Regulation of mitochondrial pyruvate carboxylation and gluconeogenesis in rat hepatocytes via an a-adrenergic adenosine 3′,5′-monophosphate-independent mechanisms, J. Biol. Chem. 254: 1129–1133.PubMedGoogle Scholar
  25. 25.
    Wakelam, M. J. O., Murphy, G. J., Hruby, V. J., and Houslay, M. D., 1986, Activation of the two signal-transduction systems in hepatocytes by glucagon, Nature (London) 323: 68–71.CrossRefGoogle Scholar
  26. 26.
    Phillips, M. J., Oshio, C., Miyairi, M., Watanabe, S., and Smith, C. R., 1983, What is actin doing in the liver? Hepatology 3: 433–436.PubMedCrossRefGoogle Scholar
  27. 27.
    Kaminski, D. L., Deshpande, Y. G., and Beinfeld, M. C., 1988, Role of glucagon in cholecystokinin-stimulated bile flow in dogs, Am. J. Physiol. 254: G864–G869.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Juan C. Sáez
    • 1
  • Michael V. L. Bennett
    • 1
  • David C. Spray
    • 1
  1. 1.Department of NeuroscienceAlbert Einstein College of MedicineBronxUSA

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