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Gene Review

GJA1  -  gap junction protein, alpha 1, 43kDa

Gallus gallus

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Disease relevance of GJA1

  • We transfected full-length or truncated chicken Cx45 into a rat osteosarcoma cell line ROS-17/2.8, which expresses endogenous Cx43 [1].

High impact information on GJA1

  • Further, we show that this ATP is released by efflux through gap junction connexin 43 hemichannels, the opening of which is evoked by spontaneous elevations of Ca2+ in trigger cells in the RPE [2].
  • Both forms of Cx45 were expressed at high levels and colocalized with Cx43 at plasma membrane junctions [1].
  • Importantly, the node and primitive streak at these stages lack Cx43 mRNA [3].
  • A survey of early expression of connexin mRNAs revealed that Cx43 is present throughout the blastoderm at Hamburger-Hamilton stage 2-3, prior to known asymmetric gene expression [3].
  • Gap junction distribution in the facial primordia of chick embryos at the time of primary palate formation was studied employing indirect immunofluorescence localization with antibodies to gap junction proteins initially identified in rat liver (27 x 10(3) Mr, connexin 32) and heart (43 x 10(3) Mr, connexin 43) [4].

Biological context of GJA1

  • Cell surface biotinylation analysis showed that surface expression of Cx43 was increased by shear stress [5].
  • We studied whether altering gap junctional communication by manipulating the relative expression of Cx43 and Cx45 affects the osteoblast phenotype [6].
  • RNA blots demonstrate that while chick connexin-43, -42, and -45 are each expressed in a number of chick organs, they each have a unique tissue distribution [7].
  • To identify connexins with potential roles in development, a chick embryo cDNA library was screened by hybridization at low stringency with a cDNA for rat connexin-43. cDNA clones for two previously undescribed connexins were isolated [7].
  • Down-regulation of Cx43 after the antisense application could be comparable to AER removal and results in distal truncation of the limb bud [8].

Anatomical context of GJA1


Associations of GJA1 with chemical compounds

  • This response was significantly reduced by antisense to Cx43 and by the gap junction and hemichannel inhibitors 18 beta-glycyrrhetinic acid and carbenoxolone, even in cells without physical contact, suggesting the involvement of Cx43-hemichannels [5].
  • Together, these results suggest fluid flow shear stress induces the translocation of Cx43 to the membrane surface and that unapposed hemichannels formed by Cx43 serve as a novel portal for the release of PGE2 in response to mechanical strain [5].
  • Cx43 gap junctions form pores that are more permeable to negatively charged dyes such as Lucifer yellow and calcein than are Cx45 pores [6].
  • Conductances between paired Xenopus oocytes injected with Cx 43, Cx 45.6 and Cx 56 mRNAs revealed that all three connexins were CO2-sensitive in this expression system [12].
  • HeLa Cx43 cells were highly invasive in controls, but did not invade the heart tissue at tumour cell aggregate-fibroblast capsule interfaces in the presence of apigenin and failed to fully engulf these heart fragments [13].

Other interactions of GJA1

  • Replacement of the N-terminus of Cx45.6 with the corresponding domain of Cx43 increased LY permeability, reduced the transjunctional voltage (V(j)) gating sensitivity, and reduced the unitary conductance of Cx45.6-43N gap junctional channels [9].

Analytical, diagnostic and therapeutic context of GJA1

  • The distribution of Connexin43 (Cx43) was examined by immunoblotting and immunofluorescence microscopy in the retinas of five different vertebrates by using a C-terminal specific peptide antibody [14].
  • We have examined the expression patterns of two members of the connexin family, connexin43 (Cx43) and connexin42 (Cx42), during the early development of the chick limb bud and embryo by in situ hybridization [15].
  • Immunoprecipitation of Cx56 from sucrose gradient fractions resulted in co-precipitation of Cx43 from NRK-Cx56 cells suggesting the presence of relatively stable interactions between the two connexins [16].
  • METHODS: We used an antipeptide antibody to connexin 43 in immunolocalization studies and an anti-peptide antibody to an external loop domain common to most connexins in Western blotting of total heart protein to measure the accumulation of connexins in the heart as it develops from 33 hours to 21 days (hatching), and in the adult [17].


  1. Transfected connexin45 alters gap junction permeability in cells expressing endogenous connexin43. Koval, M., Geist, S.T., Westphale, E.M., Kemendy, A.E., Civitelli, R., Beyer, E.C., Steinberg, T.H. J. Cell Biol. (1995) [Pubmed]
  2. ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation. Pearson, R.A., Dale, N., Llaudet, E., Mobbs, P. Neuron (2005) [Pubmed]
  3. Gap junction-mediated transfer of left-right patterning signals in the early chick blastoderm is upstream of Shh asymmetry in the node. Levin, M., Mercola, M. Development (1999) [Pubmed]
  4. Analysis of distribution patterns of gap junctions during development of embryonic chick facial primordia and brain. Minkoff, R., Parker, S.B., Hertzberg, E.L. Development (1991) [Pubmed]
  5. Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Cherian, P.P., Siller-Jackson, A.J., Gu, S., Wang, X., Bonewald, L.F., Sprague, E., Jiang, J.X. Mol. Biol. Cell (2005) [Pubmed]
  6. Gap junctional communication modulates gene expression in osteoblastic cells. Lecanda, F., Towler, D.A., Ziambaras, K., Cheng, S.L., Koval, M., Steinberg, T.H., Civitelli, R. Mol. Biol. Cell (1998) [Pubmed]
  7. Molecular cloning and developmental expression of two chick embryo gap junction proteins. Beyer, E.C. J. Biol. Chem. (1990) [Pubmed]
  8. Gap junction signalling mediated through connexin-43 is required for chick limb development. Makarenkova, H., Patel, K. Dev. Biol. (1999) [Pubmed]
  9. Role of the N-terminus in permeability of chicken connexin45.6 gap junctional channels. Dong, L., Liu, X., Li, H., Vertel, B.M., Ebihara, L. J. Physiol. (Lond.) (2006) [Pubmed]
  10. The highly conserved Gln49 and Ser50 of mammalian connexin43 are present in chick connexin43 and essential for functional gap junction channels. Sokolova, I.V., Martinez, A.M., Fletcher, W.H. Cell Commun. Adhes. (2002) [Pubmed]
  11. Differential expression of connexin 43 in the chick tangential vestibular nucleus. Popratiloff, A., Pollack, S.M., Giaume, C., Peusner, K.D. J. Neurosci. Res. (2003) [Pubmed]
  12. Changes in connexin expression and distribution during chick lens development. Jiang, J.X., White, T.W., Goodenough, D.A. Dev. Biol. (1995) [Pubmed]
  13. Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro. Czyz, J., Madeja, Z., Irmer, U., Korohoda, W., Hülser, D.F. Int. J. Cancer (2005) [Pubmed]
  14. Distribution of connexin43 immunoreactivity in the retinas of different vertebrates. Janssen-Bienhold, U., Dermietzel, R., Weiler, R. J. Comp. Neurol. (1998) [Pubmed]
  15. Expression patterns of mRNAs for the gap junction proteins connexin43 and connexin42 suggest their involvement in chick limb morphogenesis and specification of the arterial vasculature. Dealy, C.N., Beyer, E.C., Kosher, R.A. Dev. Dyn. (1994) [Pubmed]
  16. Heteromeric connexons formed by the lens connexins, connexin43 and connexin56. Berthoud, V.M., Montegna, E.A., Atal, N., Aithal, N.H., Brink, P.R., Beyer, E.C. Eur. J. Cell Biol. (2001) [Pubmed]
  17. Developmental expression of connexins in the chick embryo myocardium and other tissues. Wiens, D., Jensen, L., Jasper, J., Becker, J. Anat. Rec. (1995) [Pubmed]
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