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).
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Bennett, M. V. L., and Spray, D. C., (Eds.), 1985, Gap Junctions, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
Unwin, P. N. T., and Ennis, P. D., 1984, Two configurations of the channel-forming membrane protein, Nature (London) 307: 609–613.
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.
Hertzberg, E. L., 1984, A detergent-independent procedure for the isolation from rat liver, J. Biol. Chem. 259: 9936–9943.
Paul, D., 1986, Molecular cloning of cDNA for rat liver gap junction protein, J. Cell Biol. 103: 123–134.
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.
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.
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.
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.
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.
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.
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.
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.
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.)
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.
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.
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.
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.
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.
Graf, J., and Petersen, O. H., 1978, Cell membrane potential and resistance in liver, J. Physiol. 284: 105–126.
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.
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.
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.
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.
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.
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.
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.
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© 1990 Plenum Press, New York
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Sáez, J.C., Bennett, M.V.L., Spray, D.C. (1990). Hepatocyte Gap Junctions: Metabolic Regulation and Possible Role in Liver Metabolism. In: Hidalgo, C., Bacigalupo, J., Jaimovich, E., Vergara, J. (eds) Transduction in Biological Systems. Series of the Centro de Estudios Científicos de Santiago. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5736-0_16
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