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Gene Review

GJC1  -  gap junction protein, gamma 1, 45kDa

Homo sapiens

Synonyms: CX45, Connexin-45, Cx45, GJA7, Gap junction alpha-7 protein, ...
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Disease relevance of GJA7


High impact information on GJA7

  • The latter effect, which was caused by an increase in single-channel activity but not in unitary conductance of Cx45 channels, was not prevented by exposing CFTR-expressing cells to a Cl- channel blocker [5].
  • Both cell lines expressed connexin45 (Cx45), as evidenced by RT-PCR, immunocytochemistry, and dual patch-clamp recording [5].
  • These studies suggest that gap junction communication mediated by either Cx43 or Cx45 does not allow passage of IP3 well enough to elicit release of intracellular calcium stores in neighboring cells [6].
  • Coupling asymmetry of heterotypic connexin 45/ connexin 43-EGFP gap junctions: properties of fast and slow gating mechanisms [7].
  • Downregulation of connexin 45 gene products during mouse heart development [8].

Biological context of GJA7

  • In contrast, the Cx45 protein was constantly expressed through follicular development; however, after ovulation, no staining of Cx45 was detected in the corpus luteum [9].
  • Overall, our data show increased Cx45 in SHR that is unlikely to be due to either elevated blood pressure or to angiotensin [4].
  • Cx45 might be one of the genetic modifiers that can cause variations in the phenotype of connexin40-deficient animals [10].
  • Connexin40 (Cx40) and connexin45 (Cx45) are involved in both cardiac morphogenesis and propagation of electrical activity [10].
  • We found that Cx40/Cx45 double deficiency (Cx40(-/-)/Cx45(+/-)) causes a variety of cardiac defects leading to high mortality during embryonic development and at birth [10].

Anatomical context of GJA7

  • We used cell lines expressing wild-type connexin 45 (Cx45) and connexin 43 fused with enhanced green fluorescent protein (Cx43-EGFP) to examine mechanisms of gating in homo- and heterotypic GJs formed of these connexins [7].
  • Cx45 was localized to the detrusor layer, with Cx 43 more evident in the suburothelial mucosa [11].
  • These channels consist of structurally related transmembrane proteins, the connexins, three of which (CX43, CX40 and CX45) have been shown to be associated with the myocytes of mammalian heart; a fourth, CX37, was detected exclusively in endothelial cells [12].
  • Our data suggest that Cx45 is transcribed, expressed, and forms functional gap junction channels in rat cerebral arterial smooth muscle [13].
  • Immunostaining indicated that at 5 dyn/cm(2), the distribution of Cx43, Cx45, and ZO-1 was moderately disrupted at cell membranes; at 20 dyn/cm(2), disruption was more severe [14].

Associations of GJA7 with chemical compounds

  • Dye-coupling experiments showed that HeLa-Cx43(His)(6) cells readily passed Lucifer yellow and N-(2-aminoethyl)biotinamide hydrochloride (neurobiotin); in contrast, HeLa-Cx45 and HeLa-Cx43(His)(6)/Cx45 cells showed extensive intercellular passage of neurobiotin but little coupling with Lucifer yellow [15].
  • No correlations between the 17 beta-estradiol or progesterone serum levels and the expression patterns of the connexins Cx43, Cx45 and Cx26 could be observed [16].
  • Moreover, Cx45 nonjunctional hemichannels appeared to mediate lucifer yellow (LY) and propidium iodide (PI) dye uptake from the external solution when extracellular Ca(2+) level was reduced [17].
  • Furthermore, a set of samples was fixed with Bouin's solution, embedded in paraffin and used for immunohistochemistry with a polyclonal antibody against connexin 45 as well as for in situ hybridization studies with digoxigenin labeled connexin 45 riboprobes [18].
  • Pulse-chase experiments with the different transfectants revealed an increased turnover of Cx45, when one or both of the serine residues at positions 381 and 382 or 384 and 385 were exchanged for other amino acids [19].

Physical interactions of GJA7

  • We found that Cx43, Cx45 and Cx45t34 co-precipitated with ZO-1 in these cells, while Cx45t37 did not [20].

Co-localisations of GJA7

  • Because connexin45 (Cx45) has been shown to colocalize with Cx43, we determined whether the number, size, or distribution of Cx45 gap junctions is altered in the failing heart [2].

Other interactions of GJA7

  • Cx45/Cx43 junctions are likely to be found in brain and heart and may mediate rectifying electrical transmission or modulatable chemical communication [7].
  • Cx45 was detectable only at very low levels, with a trend toward higher levels in the atria than the ventricles in a pattern similar to Cx40 [21].
  • Valve ICs did not express connexin-32 and -40; however, connexin-26 and -43 were equally expressed by a low percentage of ICs, demonstrating cell surface and cytoplasmic expression ,and connexin-45 was weakly expressed [22].
  • Cx45 was isolated with a 220-kDa protein that we identified as ZO-1 [23].
  • This paper describes how a fluorescent nuclear tracer, Po-pro-1, can be used to visualize coupled cells in several types of retinal neurons thought to be comprised of different connexin proteins including Cx36, Cx45, Cx50, and Cx57 [24].

Analytical, diagnostic and therapeutic context of GJA7


  1. Expression of cell adhesion molecules and connexins in gap junctional intercellular communication deficient human mesothelioma tumour cell lines and communication competent primary mesothelial cells. Pelin, K., Hirvonen, A., Linnainmaa, K. Carcinogenesis (1994) [Pubmed]
  2. Up-regulation of connexin45 in heart failure. Yamada, K.A., Rogers, J.G., Sundset, R., Steinberg, T.H., Saffitz, J.E. J. Cardiovasc. Electrophysiol. (2003) [Pubmed]
  3. Hibernator Citellus undulatus maintains safe cardiac conduction and is protected against tachyarrhythmias during extreme hypothermia: possible role of Cx43 and Cx45 up-regulation. Fedorov, V.V., Li, L., Glukhov, A., Shishkina, I., Aliev, R.R., Mikheeva, T., Nikolski, V.P., Rosenshtraukh, L.V., Efimov, I.R. Heart rhythm : the official journal of the Heart Rhythm Society. (2005) [Pubmed]
  4. Increase in Cx45 gap junction channels in cerebral smooth muscle cells from SHR. Li, X., Simard, J.M. Hypertension (2002) [Pubmed]
  5. Defective regulation of gap junctional coupling in cystic fibrosis pancreatic duct cells. Chanson, M., Scerri, I., Suter, S. J. Clin. Invest. (1999) [Pubmed]
  6. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells. Jorgensen, N.R., Geist, S.T., Civitelli, R., Steinberg, T.H. J. Cell Biol. (1997) [Pubmed]
  7. Coupling asymmetry of heterotypic connexin 45/ connexin 43-EGFP gap junctions: properties of fast and slow gating mechanisms. Bukauskas, F.F., Angele, A.B., Verselis, V.K., Bennett, M.V. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Downregulation of connexin 45 gene products during mouse heart development. Alcoléa, S., Théveniau-Ruissy, M., Jarry-Guichard, T., Marics, I., Tzouanacou, E., Chauvin, J.P., Briand, J.P., Moorman, A.F., Lamers, W.H., Gros, D.B. Circ. Res. (1999) [Pubmed]
  9. Colocalization of connexin 43 and connexin 45 but absence of connexin 40 in granulosa cell gap junctions of rat ovary. Okuma, A., Kuraoka, A., Iida, H., Inai, T., Wasano, K., Shibata, Y. J. Reprod. Fertil. (1996) [Pubmed]
  10. Cardiac morphogenetic defects and conduction abnormalities in mice homozygously deficient for connexin40 and heterozygously deficient for connexin45. Kr??ger, O., Maxeiner, S., Kim, J.S., van Rijen, H.V., de Bakker, J.M., Eckardt, D., Tiemann, K., Lewalter, T., Ghanem, A., L??deritz, B., Willecke, K. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  11. Impedance measurements and connexin expression in human detrusor muscle from stable and unstable bladders. Sui, G.P., Coppen, S.R., Dupont, E., Rothery, S., Gillespie, J., Newgreen, D., Severs, N.J., Fry, C.H. BJU international. (2003) [Pubmed]
  12. Connexins in mammalian heart function. Gros, D.B., Jongsma, H.J. Bioessays (1996) [Pubmed]
  13. Connexin45 gap junction channels in rat cerebral vascular smooth muscle cells. Li, X., Simard, J.M. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  14. Fluid shear stress remodels expression and function of junctional proteins in cultured bone cells. Thi, M.M., Kojima, T., Cowin, S.C., Weinbaum, S., Spray, D.C. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  15. Connexin43 and connexin45 form heteromeric gap junction channels in which individual components determine permeability and regulation. Martinez, A.D., Hayrapetyan, V., Moreno, A.P., Beyer, E.C. Circ. Res. (2002) [Pubmed]
  16. Expression of the gap junction connexins Cx43, Cx45 and Cx26 in human uterine leiomyomata. Regidor, P.A., Engel, K., Regidor, M., Grümmer, R., Traub, O., Winterhager, E., Schindler, A.E. Gynecol. Endocrinol. (2001) [Pubmed]
  17. Biophysical properties of connexin-45 gap junction hemichannels studied in vertebrate cells. Valiunas, V. J. Gen. Physiol. (2002) [Pubmed]
  18. Evidence of gap junctions in the stable nonobstructed human bladder. John, H., Wang, X., Wehrli, E., Hauri, D., Maake, C. J. Urol. (2003) [Pubmed]
  19. Phosphorylated carboxy terminal serine residues stabilize the mouse gap junction protein connexin45 against degradation. Hertlein, B., Butterweck, A., Haubrich, S., Willecke, K., Traub, O. J. Membr. Biol. (1998) [Pubmed]
  20. Association with ZO-1 correlates with plasma membrane partitioning in truncated Connexin45 mutants. Laing, J.G., Koval, M., Steinberg, T.H. J. Membr. Biol. (2005) [Pubmed]
  21. Chamber-related differences in connexin expression in the human heart. Vozzi, C., Dupont, E., Coppen, S.R., Yeh, H.I., Severs, N.J. J. Mol. Cell. Cardiol. (1999) [Pubmed]
  22. Characterization of molecules mediating cell-cell communication in human cardiac valve interstitial cells. Latif, N., Sarathchandra, P., Taylor, P.M., Antoniw, J., Brand, N., Yacoub, M.H. Cell Biochem. Biophys. (2006) [Pubmed]
  23. Connexin45 interacts with zonula occludens-1 and connexin43 in osteoblastic cells. Laing, J.G., Manley-Markowski, R.N., Koval, M., Civitelli, R., Steinberg, T.H. J. Biol. Chem. (2001) [Pubmed]
  24. A novel fluorescent tracer for visualizing coupled cells in neural circuits of living tissue. Hoshi, H., O'brien, J., Mills, S.L. J. Histochem. Cytochem. (2006) [Pubmed]
  25. Molecular cloning of two human cardiac gap junction proteins, connexin40 and connexin45. Kanter, H.L., Saffitz, J.E., Beyer, E.C. J. Mol. Cell. Cardiol. (1994) [Pubmed]
  26. pH sensitivity of the cardiac gap junction proteins, connexin 45 and 43. Hermans, M.M., Kortekaas, P., Jongsma, H.J., Rook, M.B. Pflugers Arch. (1995) [Pubmed]
  27. Presence of functional gap junctions in human embryonic stem cells. Wong, R.C., Pébay, A., Nguyen, L.T., Koh, K.L., Pera, M.F. Stem Cells (2004) [Pubmed]
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