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.
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References
Schneider MD: Myocardial infarction as a problem of growth control: Cell cycle therapy for cardiac myocytes? J Card Fail 2: 259-263, 1996
Lampe PD, Lau AF: Regulation of gap junctions by phosphorylation of connexins. Arch Biochem Biophys 384: 205-215, 2000
Yamasaki H, Naus CC: Role of connexin genes in growth control. Carcinogenesis 17: 1199-1213, 1996
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, 1990
Beyer EC: Gap junctions. Int Rev Cytol: 1-37, 1993
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, 1998
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, 1995
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, 1987
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, 1996
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, 2000
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, 1989
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, 2001
Ai Z, Fischer A, Spray DC, Brown AM, Fishman GI: Wnt-1 regulation of connexin43 in cardiac myocytes. J Clin Invest 105: 161-171, 2000
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Dang, X., Doble, B.W. & Kardami, E. The carboxy-tail of connexin-43 localizes to the nucleus and inhibits cell growth. Mol Cell Biochem 242, 35–38 (2003). https://doi.org/10.1023/A:1021152709313
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DOI: https://doi.org/10.1023/A:1021152709313