Skip to main content

Molecular Biology of Gap Junction Proteins

  • Chapter
Molecular Biology of Diabetes

Abstract

Virtually every animal cell type forms gap junctions, the specialized regions of the cell membrane where adjacent cells concentrate channels for direct cell-to-cell exchanges of cytoplasmic ions and small molecules (1–4). Although the structure, tissue distribution and biophysical characteristics of gap junctions as well as the regulation of the intercellular communications they mediate have been the subject of numerous studies in the last three decades, an indepth analysis of the biochemistry of the proteins comprising gap junctions and of the molecular biology of the encoding genes has been possible only in the last few years (2–4). These recent developments have not completely elucidated all the intriguing questions which are raised by the existence of direct exchanges of cytoplasmic constituents between nearby cells, particularly inasmuch as the physiological function and meaning of these exchanges is concerned. However, they have clearly identified gap junction proteins as the members of amultigene family of highly conserved molecules, which have rather unique characteristics and are essentially ubiquitous in multicellular, mesozoa, and metazoa organisms (2–4).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Loewenstein WR: Junctional intercellular communication. The cell-to-cell membrane channel. Physiol Rev 61:829–913, 1981.

    Google Scholar 

  2. Bennett MVL, Barrio LC, Bargiello TA, Spray DC, Hertzberg E, Saez JC: Gap junctions: New tools, new answers, new questions. Neuron 6:305–320, 1991.

    Article  Google Scholar 

  3. Kumar NM, Gilula NB: Molecular biology and genetics of gap junction channels. Sem Cell Biol 3:3–16, 1992.

    Article  Google Scholar 

  4. Beyer EC: Gap junctions. Int Rev Cytol 137C: 1–37, 1993.

    Google Scholar 

  5. Orci L, Unger RH, Renold AE: Structural coupling between pancreatic islet cells. Experientia 29:1015–1018, 1973.

    Article  Google Scholar 

  6. Meda P, Bosco D, Giordano E, Chanson M: Junctional coupling modulation by secretagogues in two-cell pancreatic systems. In Biophysics of Gap Junction Channels, Peracchia C, ed. CRC, Boca Raton, FL, pp. 191–208, 1991.

    Google Scholar 

  7. Meda P: Gap junctional coupling and secretion in endocrine and exocrine pancreas. In Cell Interactions and Gap Junctions, Sperelakis N, Cole WC, eds. CRC, Boca Raton, FL, pp. 59–83, 1989.

    Google Scholar 

  8. Revel J-P, Karnovsky MJ: Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J Cell Biol 33:C7–C12, 1967.

    Article  Google Scholar 

  9. Bullivant S: Freeze-fracturing of biological materials. Micron 1:46–51, 1969.

    Article  Google Scholar 

  10. Makowski L, Caspar DL, Phillips WC, Goodenough DA: Gap junction structures. II. Analysis of the x-ray diffraction data. J Cell Biol 74:629–645, 1977.

    Article  Google Scholar 

  11. Goodenough DA, Paul DL, Jesaitis L: Topological distribution of two connexin32 antigenic sites in intact and split rodent hepatocyte gap junctions. J Cell Biol 107:1817–1824, 1988.

    Article  Google Scholar 

  12. Unwin PNT, Ennis PD: Two configurations of a channel-forming membrane protein. Nature (London) 307:609–613, 1984.

    Article  Google Scholar 

  13. Beyer EC, Paul DL, Goodenough DA: Connexin family of gap junction proteins. J Membr Biol 116:187–194, 1990.

    Article  Google Scholar 

  14. Willecke K, Hennemann H, Dahl E, Jungbluth S, Heynkes R: The diversity of connexin genes encoding gap junctional proteins. Eur J Cell Biol 56:1–7, 1991.

    Google Scholar 

  15. Werner R, Miller T, Azarnia R, Dahl G: Translation and functional expression of cell-cell channel mRNA in Xenopus oocytes. J Membr Biol 87:253–268, 1985.

    Article  Google Scholar 

  16. Bruzzone R, Haefliger J-A, Gimlich RL, Paul DL: Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell 4:7–20, 1993.

    Google Scholar 

  17. Schwarzmann G, Wiegandt H, Rose B, Zimmerman A, BenHaim D, Loewenstein WR: Diameter of the cell-to-cell junctional membrane channels as probed with neutral molecules. Science 213:551–553, 1981.

    Article  Google Scholar 

  18. Zimmer DB, Green CR, Evans WH, Gilula NB: Topological analysis of the major protein in isolated intact rat liver gap junctions and gap junction-derived single-membrane structures. J Biol Chem 262:7751–7763, 1987.

    Google Scholar 

  19. Kumar NM, Gilula NB: Cloning and characterization of human and rat liver cDNAs coding for a gap junction protein. J Cell Biol 103:767–776, 1986.

    Article  Google Scholar 

  20. Paul D: Molecular cloning of cDNA for rat liver gap junction protein. J Cell Biol 103:123–134, 1986.

    Article  Google Scholar 

  21. Beyer EC, Paul DL, Goodenough DA: Connexin 43: A protein from rat heart homologous to a gap junction protein from liver. J Cell Biol 105:2621–2629, 1987.

    Article  Google Scholar 

  22. Zhang J-T, Nicholson BJ: Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx 26, as deduced from its cDNA. J Cell Biol 109:3391–3401, 1989.

    Article  Google Scholar 

  23. Dupont E, El Aoumari A, Briand JP, Fromaget C, Gros D: Cross linking of cardiac gap junction connexons by thiol/disulfide exchanges. J Membr Biol 108:247–252, 1989.

    Article  Google Scholar 

  24. Sáez JC, Spray DC, Nairn AC, Hertzberg EL, Greengard P, Bennett MVL: cAMP increases junctional conductance and stimulates phosphorylation of the 27-kDa principal gap junction polypeptide. Proc Nail Acad Sci USA 83:2473–2477, 1986.

    Article  Google Scholar 

  25. Musil LS, Beyer EC, Goodenough DA: Expression of the gap junction protein connexin 43 in embryonic chick lens: molecular cloning, ultrastructural localization, and post-translational phosphorylation. J Membr Biol 116:163–175,1990.

    Article  Google Scholar 

  26. Gimlich RL, Kumar NM, Gilula NB: Sequence and developmental expression of mRNA coding for a gap junction protein in Xenopus. J Cell Biol 107:1065–1073, 1988.

    Article  Google Scholar 

  27. Crow DS, Beyer EC, Paul DL, Kobe SS, Lau AF: Phosphorylation of connexin43 gap junction protein in uninfected and Rous sarcoma virus-transformed mammalian fibroblasts. Mol Cell Biol 10:1754–1763, 1990.

    Google Scholar 

  28. Miller T, Dahl G, Werner R: Structure of a gap junction gene: rat connexin 32. Biosci Rep 8:455–464, 1988.

    Article  Google Scholar 

  29. Fishman GI, Eddy RL, Shows TB, Rosenthal L, Leinwand LA: The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structure. Genomics 10:250–256, 1991.

    Article  Google Scholar 

  30. Hennemann H, Kozjek G, Dahl E, Nicholson B, Willecke K: Molecular cloning of mouse connexins26 and-32: similar genomic organization but distinct promoter sequences of two gap junction genes. Eur J Cell Biol 58:81–89, 1992.

    Google Scholar 

  31. Hsieh C-L, Kumar NM, Gilula NB, Francke U: Distribution of genes for gap junction membrane channel proteins on human and mouse chromosomes. Somatic Cell Mol Genet 17:191–200, 1991.

    Article  Google Scholar 

  32. Hooper ML, Subak-Sharpe JH: Metabolic co-operation between cells. Int Rev Cytol 69:46–104, 1981.

    Google Scholar 

  33. Kohen E, Kohen C, Thorell B, Mintz DH, Rabinovitch A: Intercellular communication in pancreatic islet monolayer cultures: a microfluorometric study. Science 204:862–865, 1979.

    Article  Google Scholar 

  34. Stewart WW: Functional connections between cells as revealed by dye-coupling with a highly fluorescent naphthalimide tracer. Cell 14:741–759, 1978.

    Article  Google Scholar 

  35. Vaney DI: Many diverse types of retinal neurons show tracer coupling when injected with biocytin or Neurobiotin. Neurosc Let 125:187–190, 1991.

    Article  Google Scholar 

  36. Meda P, Spray DC: Gap junction function. In Adv Mol Cell Biol, in press.

    Google Scholar 

  37. Meda P, Perrelet A, Orci L: Gap junctions and cell-to-cell coupling in endocrine glands. Mod Cell Biol 3:131–196, 1984.

    Google Scholar 

  38. Meda P, Pepper M, Traub O, Willecke K, Gros D, Beyer E, Nicholson B, Paul D, Orci L: Differential expression of gap junction connexins in endocrine and exocrine glands. Endocrinology 133:2371–2378, 1993.

    Article  Google Scholar 

  39. Ullrich S, Vozzi C, Meda P: Connexins of insulin-secreting cells: Quantification of mRNA by polymerase chain reaction. Diabetologia 36(Suppl 1):A5, 1993.

    Google Scholar 

  40. Meda P, Chanson M, Pepper M, Giordano E, Bosco D, Traub O, Willecke K, El Aoumari A, Gros D, Beyer E, Orci L, Spray DC: In vivo modulation of connexin 43 gene expression and junctional coupling of pancreatic B-cells. Exp Cell Res 192:469–480, 1991.

    Article  Google Scholar 

  41. Meda P, Perrelet A, Orci L: Increase of gap junctions between pancreatic B-cells during stimulation of insulin secretion. J Cell Biol 82:441–448, 1979.

    Article  Google Scholar 

  42. Eddlestone GT, Gonçalves A, Bangham JA, Rojas E: Electrical coupling between cells in islets of Langerhans from mouse. J Membr Biol 77:1–14, 1984.

    Article  Google Scholar 

  43. Meda P, Amherdt M, Perrelet A, Orci L: Metabolic coupling between cultured pancreatic B-cells. Exp Cell Res 133:421–430, 1981.

    Article  Google Scholar 

  44. Meda P, Michaels RL, Halban PA, Orci L, Sheridan JD: In vivo modulation of gap junctions and dye coupling between B-cells of the intact pancreatic islet. Diabetes 32:858–868, 1983.

    Article  Google Scholar 

  45. Lernmark A: The preparation of, and studies on, free cell suspensions from mouse pancreatic islets. Diabetologia 10:431–438, 1974.

    Article  Google Scholar 

  46. Salomon D, Meda P: Heterogeneity and contact-dependent regulation of hormone secretion by individual B cells. Exp Cell Res 162:507–520, 1986.

    Article  Google Scholar 

  47. Bosco D, Meda P; Actively synthetizing B-cells secrete preferentially during glucose stimulation. Endocrinology 129:3157–3166, 1992.

    Article  Google Scholar 

  48. Philippe J, Giordano E, Gjinovci A, Meda P: cAMP prevents the glucocorticoid-mediated inhibition of insulin gene expression in rodent islet cells. J Clin Invest 90:2228–2233, 1992.

    Article  Google Scholar 

  49. Meda P, Bosco D, Chanson M, Giordano E, Vallar L, Wollheim C, Orci L: Rapid and reversible secretion changes during uncoupling of rat insulin-producing cells. J Clin Invest 86:759–768, 1990.

    Article  Google Scholar 

  50. Kohen E, Kohen C, Rabinovitch A: Cell-to-cell communication in rat pancreatic islet monolayer cultures is modulated by agents affecting islet cell secretory activity. Diabetes 32:95–98, 1983.

    Article  Google Scholar 

  51. Appel MC, O’Neill, JJ, Meda P: Effects of glucose on islet gap junctional communication. Diabetes 37(suppl 1) 47A, 1988.

    Google Scholar 

  52. Bruzzone R, Meda P: The gap junction: a channel for multiple functions? Eur J Clin Invest 18:444–453, 1988.

    Article  Google Scholar 

  53. Vozzi C, Ullrich S, Bosco D, Dupont E, Meda P: Glucose-unresponsive insulin-producing cells show defects in gap junction coupling and improved secretion after Cx43 transfection. Acta Anat, in press.

    Google Scholar 

  54. Sorenson RL, Parsons JA: Insulin secretion in mammosomatotropic tumor-bearing and pregnant rats. A role for lactogens. Diabetes 34:338–341, 1985.

    Article  Google Scholar 

  55. Santos RM, Rosario LM, Ndala A, Garcia-Sancho J, Soria B, Valdeomillos M: Widespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets. Pflugers Arch 418:417–422, 1991.

    Article  Google Scholar 

  56. Gylfe E, Grapengiesser E, Hellman B: Propagation of cytoplasmic Ca2+ oscillations in clusters of pancreatic β-cells exposed to glucose. Cell Calcium 12:229–240, 1991.

    Article  Google Scholar 

  57. Soria B, Chanson M, Giordano E, Bosco D, Meda P: Ion channels of glucose-responsive and-unresponsive B-cells. Diabetes 40: 1069–1078, 1991

    Article  Google Scholar 

  58. Schuit FC, In’tVeld PA, Pipeleers DG: Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells. Proc Natl Acad Sci USA 85:3865–3869, 1988.

    Article  Google Scholar 

  59. Kiekens R, In’tVeld P, Mahler T, Schuit F, Van De Winkel M, Pipeleers D: Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differencesin glucose-induced biosynthetic activity. J Clin Invest 89:117–125, 1992.

    Article  Google Scholar 

  60. Atwater I, Rosario L, Rojas E: Properties of the Ca-activated K+ channel in pancreatic B-cells. Cell calcium 4:451–461, 1983.

    Article  Google Scholar 

  61. Lawrence TS, Beers WH, Gilula NB: Transmission of hormonal stimulation by cell-to-cell communication. Nature 272:501–506, 1978.

    Article  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Meda, P. (1994). Molecular Biology of Gap Junction Proteins. In: Draznin, B., LeRoith, D. (eds) Molecular Biology of Diabetes. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0241-7_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-0241-7_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-6677-8

  • Online ISBN: 978-1-4612-0241-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics