Journal of Membrane Biology

, Volume 217, Issue 1–3, pp 5–12 | Cite as

Introduction: A Tribute to Cell-to-Cell Channels




I thank Werner for introducing me to cell-to-cell channels and giving me a chance to work and explore them. I thank Birgit Rose for her friendship and Kamlesh Asotra for critical reading of the manuscript on short notice and for his friendship. I also thank Richard G. MacDonald for his instructive comments on the manuscript. I apologize for not citing, due to space limitation, important work of many investigators who have also made contributions to this field. Current research in my laboratory is supported by the National Institutes of Health (CA 113903) and the Nebraska Health and Human Service System (LB 506).


  1. Balda MS, Matter K (2004) Epithelial cell adhesion and the regulation of gene expression. Trends Cell Biol 13:310–318CrossRefGoogle Scholar
  2. Berthoud VM, Minogue PJ, Laing JG, Beyer EC (2004) Pathways for degradation of connexins and gap junctions. Cardiovasc Res 62:256–267PubMedCrossRefGoogle Scholar
  3. Braga VM (2002) Cell-cell adhesion and signalling. Curr Opin Cell Biol 14:546–556PubMedCrossRefGoogle Scholar
  4. Evans WH, Martin PEM (2002) Lighting up gap junction channels in a flash. Bioessays 24:876–880PubMedCrossRefGoogle Scholar
  5. Goodenough DA, Goliger JA, Paul DA (1996) Connexins, connexons, and intercellular communication. Annu Rev Biochem 65:475–502PubMedCrossRefGoogle Scholar
  6. Gumbiner BM (2000) Regulation of cadherin adhesive-activity. J Cell Biol 148:399–404PubMedCrossRefGoogle Scholar
  7. Gumbiner BM (2005) Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 6:622–634PubMedCrossRefGoogle Scholar
  8. Harris AL (2001) Emerging issues of connexin channels: biophysics fills the gap. Q Rev Biophys 34:325–472PubMedGoogle Scholar
  9. Hunter T (2000) Signaling – 2000 and beyond. Cell 100:113–127PubMedCrossRefGoogle Scholar
  10. Johnson RG, Hammer J, Sheridan JD, Revel J-P (1974) Gap junction formation between reaggregated Novikoff hepatoma cells. Proc Natl Acad Sci USA 71:4536–4543PubMedCrossRefGoogle Scholar
  11. Kanno Y, Loewenstein WR (1964a) Intercellular diffusion. Science 143:959–960Google Scholar
  12. Kanno Y, Loewenstein WR (1964b) Low resistance coupling between gland cells. Some observations on the intercellular contact membranes and intercellular space. Nature 201:194–195Google Scholar
  13. Kanno Y, Loewenstein WR (1966) Cell-to-cell passage of large molecules. Nature 212:629PubMedCrossRefGoogle Scholar
  14. Kelsell DP, Di W-L, Houseman MJ (2001) Connexin mutations in skin disease and hearing loss. Am J Hum Genet 68:559–568PubMedCrossRefGoogle Scholar
  15. King TJ, Gurley KE, Prunty J, Shin JL, Kemp CJ, Lampe PD (2005) Deficiency in the gap junction protein connexin32 alters p27Kip1 tumor suppression and MAPK activation in a tissue-specific manner. Oncogene 24:1718–1726PubMedCrossRefGoogle Scholar
  16. King TJ, Lampe PD (2004a) Mice deficient for the gap junction protein connexin32 exhibit increased radiation-induced tumorigenesis associated with elevated mitogen-activated protein kinase (p44/Erk1, p42/Erk2) activation. Carcinogen 25:669–680Google Scholar
  17. King TJ, Lampe PD (2004b) The gap junction protein connexin32 is a mouse lung tumor suppressor. Cancer Res 64:7191–7196Google Scholar
  18. Kojima T, Kokai Y, Chiba H, Yamamoto M, Mochizuki Y, Sawada N (2001) Cx32 but not Cx26 is associated with tight junctions in primary cultures of rat hepatocytes. Biochem Biophys Res Commun 263:193–201Google Scholar
  19. Kojima T, Spray DC, Kokai Y, Chiba H, Mochizuki Y, Sawada N (2002) Cx32 formation and/or Cx32-mediated intercellular communication induces expression and function of tight junctions in hepatocytic cell line. Exp Cell Res 276:40–51PubMedCrossRefGoogle Scholar
  20. Krutovskikh V, Yamasaki H (2000) Connexin gene mutations in human genetic diseases. Mutat Res 462:197–207PubMedCrossRefGoogle Scholar
  21. Kumar NM, Gilula NB (1996) The gap junction communication channel. Cell 84:381–388PubMedCrossRefGoogle Scholar
  22. Laird DW (2006) Life cycle of connexins in health and disease. Biochem J 394:527–543PubMedCrossRefGoogle Scholar
  23. Lampe PD, Lau AF (2000) Regulation of gap junctions by phosphorylation of connexins. Arch Biochem Biophys 384:205–215PubMedCrossRefGoogle Scholar
  24. Lo CW (1989) Communication compartments: a conserved role in pattern formation? In: Sperelakis N, Cole WC (eds) Cell interactions and gap junctions. CRC, Boca Raton, FL, pp 86–96Google Scholar
  25. Lo CW, Gilula NB (1979) Gap junctional communication in post-implantation mouse embryo. Cell 18:411–422PubMedCrossRefGoogle Scholar
  26. Loewenstein WR (1966) Permeability of membrane junctions. Ann NY Acad Sci 137:441–472PubMedCrossRefGoogle Scholar
  27. Loewenstein WR (1967) On the genesis of cellular communication. Dev Biol 503–520Google Scholar
  28. Loewenstein WR (1968a) Communication through cell junctions: implications in growth control and differentiation. Dev Biol (Suppl 2):151–163Google Scholar
  29. Loewenstein WR (1968b) Some reflections on growth and differentiation. Perspect Biol Med 11:260–272Google Scholar
  30. Loewenstein WR (1974) Cellular communication by permeable junctions. Hosp Proc Membr Ser 9:113–122Google Scholar
  31. Loewenstein WR (1975) Permeable junctions. Cold Spring Harbor Symp Quant Biol 40:49–63Google Scholar
  32. Loewenstein WR (1979) Junctional intercellular communication and the control of growth. Biochem Biophys Acta 560:1–65PubMedGoogle Scholar
  33. Loewenstein WR (1981) Junctional intercellular communication: the cell-to-cell membrane channel. Physiol Rev 61:829–913PubMedGoogle Scholar
  34. Loewenstein WR (1989) From cell theory to cell connectivity: experiments in cell-to-cell communication. In: Tosteson DC (ed) Membrane transport: people and ideas. American Physiological Society, Bethesda, MD, pp 303–335Google Scholar
  35. Loewenstein WR, Kanno Y (1964) Studies on an epithelial (gland) cell junction. 1. Modifications of surface membrane permeability. J Cell Biol 22:565–586PubMedCrossRefGoogle Scholar
  36. Loewenstein WR, Kanno Y (1966) Intercellular communication and the control of tissue growth. Lack of communication between cancer cells. Nature 209:1248–1249PubMedCrossRefGoogle Scholar
  37. Matter K, Balda MS (2003) Signalling to and from tight junctions. Nat Rev Mol Cell Biol 4:225–236PubMedCrossRefGoogle Scholar
  38. Mehta PP, Bertram JS, Loewenstein WR (1986) Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44:187–196PubMedCrossRefGoogle Scholar
  39. Mesnil M, Crespin S, Avanzo JL, Zaidan-Dagli ML (2005) Defective gap junctional intercellular communication in the carcinogenic process. Biochim Biophys Acta 1719:125–145PubMedCrossRefGoogle Scholar
  40. Radhakrishnan S (1937) The spirit in man. In: An idealist view of life. Unwin Hyman, London, pp 138–175Google Scholar
  41. Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC (2003) Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev 83:1359–1400PubMedGoogle Scholar
  42. Segretain D, Falk MM (2004) Regulation of connexin biosynthesis, assembly, gap junction formation, and removal. Biochim Biophys Acta 1662:3–21PubMedCrossRefGoogle Scholar
  43. Sohl G, Maxeiner S, Willecke K (2005) Expression and function of neural gap junctions. Nat Rev Neurosci 6:191–200PubMedCrossRefGoogle Scholar
  44. Sosinsky GE, Nicholson BJ (2005) Structural organization of gap junction channels. Biochim Biophys Acta 1711:99–125PubMedCrossRefGoogle Scholar
  45. Temme A, Buchmann A, Gabriel H-D, Nelles E, Schwarz M, Willecke K (1997) High incidence of spontaneous and chemically induced liver tumors in mice deficient for connexin 32. Curr Biol 7:713–716PubMedCrossRefGoogle Scholar
  46. Trosko JE, Chang C-C, Madhukar BV (1994) The role of modulated gap junctional intercellular communication in epigenetic toxicology. Risk Anal 14:303–312PubMedCrossRefGoogle Scholar
  47. Trosko JE, Ruch RJ (1998) Cell-cell communication in carcinogenesis. Front Biosci 3:208–236Google Scholar
  48. Warn-Cramer BJ, Lau AF (2004) Regulation of gap junctions by tyrosine protein kinases. Biochim Biophys Acta 1662:81–95PubMedCrossRefGoogle Scholar
  49. Wei J-C, Xu X, Lo CW (2004) Connexins and cell signaling in development and disease. 20:811–838Google Scholar
  50. Weinberg RA (2007) The biology of cancer. Garland, New YorkGoogle Scholar
  51. Wheelock MJ, Johnson KR (2003a) Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol 19:207–235Google Scholar
  52. Wheelock MJ, Johnson KR (2003b) Cadherin-mediated cellular signaling. Curr Opin Cell Biol 15:509–514Google Scholar
  53. White TW, Paul DL (1999) Genetic diseases and gene knockouts reveal diverse connexin functions. Annu Rev Physiol 61:283–310PubMedCrossRefGoogle Scholar
  54. Yamasaki H, Naus CGS (1996) Role of connexin genes in growth control. Carcinogen 17:1199–1213CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaUSA

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