Advertisement

Molecular and Cellular Biochemistry

, Volume 242, Issue 1–2, pp 35–38 | Cite as

The carboxy-tail of connexin-43 localizes to the nucleus and inhibits cell growth

  • Xitong Dang
  • Bradley W. Doble
  • Elissavet Kardami
Article

Abstract

Gap junctions are plasma membrane intercellular communication channels that in addition to ensuring electrical coupling and coordinated mechanical activity, can act as growth suppressors. To define the role of a non-channel forming domain of connexin-43 (Cx43), the main constituent of cardiomyocyte gap junctions, on growth regulation, we expressed its C-terminal portion (CT-Cx43) in cardiomyocytes and HeLa cells. In addition to broad cytoplasmic localization, CT-Cx43 was also localized to the nucleus of both cell types, detected by immunofluorescence as well as immunoblotting of subcellular fractions. Furthermore, stable expression of CT-Cx43 in HeLa cells induced a significant decrease in proliferation. It is therefore suggested that plasma membrane localization and formation of channels are not required for growth inhibition by Cx43, and that nuclear localization of CT-Cx43 may exert effects on gene expression and growth.

structure-function cell proliferation gap junctions nucleus 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Schneider MD: Myocardial infarction as a problem of growth control: Cell cycle therapy for cardiac myocytes? J Card Fail 2: 259-263, 1996Google Scholar
  2. 2.
    Lampe PD, Lau AF: Regulation of gap junctions by phosphorylation of connexins. Arch Biochem Biophys 384: 205-215, 2000Google Scholar
  3. 3.
    Yamasaki H, Naus CC: Role of connexin genes in growth control. Carcinogenesis 17: 1199-1213, 1996Google Scholar
  4. 4.
    Gourdie RG, Harfst E, Severs NJ, Green CR: Cardiac gap junctions in rat ventricle: Localization using site-directed antibodies and laser scanning confocal microscopy. Cardioscience 1: 75-82, 1990Google Scholar
  5. 5.
    Beyer EC: Gap junctions. Int Rev Cytol: 1-37, 1993Google Scholar
  6. 6.
    Zhang ZQ, Zhang W, Wang NQ, Bani-Yaghoub M, Lin ZX, Naus CC: Suppression of tumorigenicity of human lung carcinoma cells after transfection with connexin43. Carcinogenesis 19: 1889-1894, 1998Google Scholar
  7. 7.
    Mesnil M, Krutovskikh V, Piccoli C, Elfgang C, Traub O, Willecke K, Yamasaki H: Negative growth control of HeLa cells by connexin genes: Connexin species specificity. Cancer Res 55: 629-639, 1995Google Scholar
  8. 8.
    Beyer EC, Paul DL, Goodenough DA: Connexin43: A protein from rat heart homologous to a gap junction protein from liver. J Cell Biol 105: 2621-2629, 1987Google Scholar
  9. 9.
    Doble BW, Chen Y, Bosc DG, Litchfield DW, Kardami E: Fibroblast growth factor-2 decreases metabolic coupling and stimulates phosphorylation as well as masking of connexin43 epitopes in cardiac myocytes. Circ Res 79: 647-658, 1996Google Scholar
  10. 10.
    Doble BW, Ping P, Kardami E: The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation. Circ Res 86: 293-301, 2000Google Scholar
  11. 11.
    Yancey SB, John SA, Lal R, Austin BJ, Revel JP: The 43-kD polypeptide of heart gap junctions: Immunolocalization, topology, and functional domains. J Cell Biol 108: 2241-2254, 1989Google Scholar
  12. 12.
    Giepmans BN, Hengeveld T, Postma FR, Moolenaar WH: Interaction of c-Src with gap junction protein connexin-43. Role in the regulation of cell-cell communication. J Biol Chem 276: 8544-8549, 2001Google Scholar
  13. 13.
    Ai Z, Fischer A, Spray DC, Brown AM, Fishman GI: Wnt-1 regulation of connexin43 in cardiac myocytes. J Clin Invest 105: 161-171, 2000Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Xitong Dang
    • 1
  • Bradley W. Doble
    • 1
  • Elissavet Kardami
    • 1
  1. 1.Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of PhysiologyUniversity of ManitobaWinnipegCanada

Personalised recommendations