The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Gja1  -  gap junction protein, alpha 1

Rattus norvegicus

Synonyms: Connexin-43, Cx43, Cxn-43, Gap junction 43 kDa heart protein, Gap junction alpha-1 protein
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Gja1


Psychiatry related information on Gja1

  • In the CN, however, Cx43 density was both increased with Huntington's disease and became located in patches [5].
  • The cardiomyocyte sheets became attached to the infarcted myocardium, showed angiogenesis, expressed connexin-43, and appeared as homogeneous tissue in the myocardium Electrophysiological experiments showed a QRS complex with one peak in the treated scar area in the T group, but two peaks, indicative of branch block, in that of the other groups [6].

High impact information on Gja1


Chemical compound and disease context of Gja1

  • Cx43 became profoundly dephosphorylated during hypoxia only when glucose supplies were limited and was completely rephosphorylated within 30 minutes of reoxygenation [1].
  • The objectives of this study were to determine the effects of propylthiouracil (PTU)-induced neonatal hypothyroidism on the gap junctional protein Cx43 in rat testis and epididymis [4].
  • This novel form of longitudinally arranged Cx 43 immunoreactivity was modified by dehydration and halothane exposure, but not lactation [3].
  • The objective of the present study was to examine the effects of the antiprogesterone RU486 on the expression levels of multiple gap junction (GJ) gene products and, in detail, on alpha 1 (connexin43 [Cx43]), in various regions of the rat implantation chamber during experimentally induced preterm labor at mid/late stages of gestation [10].
  • Geldanamycin abolished the 2-fold increase in mitochondrial Cx43 induced by 2 preconditioning cycles of ischemia/reperfusion, but this effect was not associated with reduced protection [11].

Biological context of Gja1


Anatomical context of Gja1

  • Together, our findings reveal a novel role for Cx43-mediated gap junctions, namely as conduits for the spread of proinflammatory signals in the lung capillary bed [8].
  • Labor was also associated with a coincident expression of c-fos and Cx-43 in the myometrium, although there was no change in c-jun mRNA levels during this period [16].
  • In the present study we have investigated effects of FGF-2 and of other growth factors on the expression and function of cx43 in astroglial cells cultured from telencephalic cortex, striatum, and mesencephalon of newborn rats [17].
  • As thyrocytes cultured in the form of a monolayer only express Cx43, we hypothesized that Cx32 could play a role in thyroid folliculogenesis [15].
  • Long-term up-regulation of Cx43 in reactive astrocytes may be one critical component in the rearrangement of the local astroglial network following SCI [18].

Associations of Gja1 with chemical compounds


Physical interactions of Gja1

  • Far Western analysis revealed that ZO-2 can directly bind to Cx43 independent of other interacting partners [14].
  • Immunoblot analysis of associated proteins showed that the C-terminal domain of connexin-43 binds to the N-terminal domain of ZO-1 [20].
  • Similarly, antibody against Cx40 coimmunoprecipitated Cx43 from the same connexon fraction but only Cx40 from Cx (monomer) fractions [21].

Enzymatic interactions of Gja1

  • In addition, studies with rat primary-cultured cardiomyocytes demonstrated that acetylcholine effectively prevented the hypoxia-induced loss of phosphorylated Cx43 and ameliorated the loss of cell-to-cell communication as determined by Lucifer Yellow dye transfer assay, which supports the in vivo results [22].

Co-localisations of Gja1


Regulatory relationships of Gja1

  • Moreover, in the same brain regions Cx32 and Cx43 were up-regulated in non-neruronal cells whereas the neuronal Cx36 was down-regulated [23].
  • AT-II-induced Cx43 induction could be completely inhibited by the AT1 receptor antagonist losartan [24].
  • We show herein that phagocytosis activation by LPS concomitantly stimulated Cx33 and inhibited Cx43 mRNA levels [25].
  • Stretch-induced upregulation of Cx43 expression was blocked by either anti-VEGF antibody or anti-TGF-beta antibody [26].
  • These findings indicate that alterations in Cx32 and Cx26 expression occur rapidly in hepatocytes stimulated to proliferate and that several nonparenchymal liver cell types upregulate Cx43 expression when induced to proliferate [27].

Other interactions of Gja1

  • Instead, Cx32 and Cx43 were restricted to glial gap junctions [28].
  • Among at least six gap junction-forming connexin proteins in adult rat brain, connexin- (Cx) 32, Cx36, and Cx43 have been reported to occur in neurons [28].
  • MS/MS analysis of tryptic fragments yielded several proteins including zona occludens-1 (ZO-1), a structural protein previously identified to interact with Cx43, and ZO-2, a potential novel interacting partner [14].
  • We confirmed the interaction of ZO-2 with Cx43 by using a combination of fusion protein "pull down," co-immunoprecipitation, and co-localization experiments [14].
  • Treatment of pregnant rats with progesterone beginning on day 20 (which blocks both the increase in Cx-43 expression and the onset of labor) maintained the elevated expression of Cx-26 [29].

Analytical, diagnostic and therapeutic context of Gja1

  • Using alkaline phosphatase and Western blot analyses, we identified three forms of Cx43: a nonphosphorylated form (P0) and two phosphorylated forms (P1 and P2) [13].
  • Using immunofluorescence microscopy, we observed Cx43 localization at specific sites of contact (plaques) between adjacent cells [13].
  • We have utilized tandem mass spectrometry (MS/MS) sequence analysis as a screen to identify proteins from cell lysates that interact with the C-terminal cytoplasmic region of connexin 43 (Cx43) [14].
  • These associative data were strengthened by our observation that in paradigms in which labor was induced prematurely by ovariectomy or blocked by treatment with progesterone, changes in c-fos expression were closely matched by changes in Cx-43 mRNA [16].
  • Decreases in steady-state connexin 43 mRNA levels were detected by northern blot analysis within 1 h and paralleled changes in steady-state beta-actin mRNA, but these changes did not occur rapidly enough to account for the rapid loss of gap-junction function [30].


  1. Reversible connexin 43 dephosphorylation during hypoxia and reoxygenation is linked to cellular ATP levels. Turner, M.S., Haywood, G.A., Andreka, P., You, L., Martin, P.E., Evans, W.H., Webster, K.A., Bishopric, N.H. Circ. Res. (2004) [Pubmed]
  2. Lysosomal and proteasomal degradation play distinct roles in the life cycle of Cx43 in gap junctional intercellular communication-deficient and -competent breast tumor cells. Qin, H., Shao, Q., Igdoura, S.A., Alaoui-Jamali, M.A., Laird, D.W. J. Biol. Chem. (2003) [Pubmed]
  3. Detection of a novel pattern of connexin 43 immunoreactivity responsive to dehydration in rat hypothalamic magnocellular nuclei. Eisner, I., Colombo, J.A. Exp. Neurol. (2002) [Pubmed]
  4. Neonatal hypothyroidism alters the localization of gap junctional protein connexin 43 in the testis and messenger RNA levels in the epididymis of the rat. St-Pierre, N., Dufresne, J., Rooney, A.A., Cyr, D.G. Biol. Reprod. (2003) [Pubmed]
  5. Connexin expression in Huntington's diseased human brain. Vis, J.C., Nicholson, L.F., Faull, R.L., Evans, W.H., Severs, N.J., Green, C.R. Cell Biol. Int. (1998) [Pubmed]
  6. Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium. Miyagawa, S., Sawa, Y., Sakakida, S., Taketani, S., Kondoh, H., Memon, I.A., Imanishi, Y., Shimizu, T., Okano, T., Matsuda, H. Transplantation (2005) [Pubmed]
  7. Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Musil, L.S., Goodenough, D.A. Cell (1993) [Pubmed]
  8. Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries. Parthasarathi, K., Ichimura, H., Monma, E., Lindert, J., Quadri, S., Issekutz, A., Bhattacharya, J. J. Clin. Invest. (2006) [Pubmed]
  9. Intercellular communication via gap junctions in activated rat hepatic stellate cells. Fischer, R., Reinehr, R., Lu, T.P., Schönicke, A., Warskulat, U., Dienes, H.P., Häussinger, D. Gastroenterology (2005) [Pubmed]
  10. Gap junction regulation during preterm labor in the rat: multiple effects of the antiprogesterone RU486. Risek, B., Gilula, N.B. Biol. Reprod. (1996) [Pubmed]
  11. Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Rodriguez-Sinovas, A., Boengler, K., Cabestrero, A., Gres, P., Morente, M., Ruiz-Meana, M., Konietzka, I., Miró, E., Totzeck, A., Heusch, G., Schulz, R., Garcia-Dorado, D. Circ. Res. (2006) [Pubmed]
  12. Epidermal growth factor receptor is a common mediator of quinone-induced signaling leading to phosphorylation of connexin-43: role of glutathione and tyrosine phosphatases. Abdelmohsen, K., Gerber, P.A., von Montfort, C., Sies, H., Klotz, L.O. J. Biol. Chem. (2003) [Pubmed]
  13. Downregulation of connexin 43 expression by high glucose reduces gap junction activity in microvascular endothelial cells. Sato, T., Haimovici, R., Kao, R., Li, A.F., Roy, S. Diabetes (2002) [Pubmed]
  14. Connexin 43 interacts with zona occludens-1 and -2 proteins in a cell cycle stage-specific manner. Singh, D., Solan, J.L., Taffet, S.M., Javier, R., Lampe, P.D. J. Biol. Chem. (2005) [Pubmed]
  15. Formation of three-dimensional thyroid follicle-like structures by polarized FRT cells made communication competent by transfection and stable expression of the connexin-32 gene. Tonoli, H., Flachon, V., Audebet, C., Callé, A., Jarry-Guichard, T., Statuto, M., Rousset, B., Munari-Silem, Y. Endocrinology (2000) [Pubmed]
  16. Increase in messenger ribonucleic acid encoding the myometrial gap junction protein, connexin-43, requires protein synthesis and is associated with increased expression of the activator protein-1, c-fos. Piersanti, M., Lye, S.J. Endocrinology (1995) [Pubmed]
  17. Fibroblast growth factor 2 (FGF-2) differentially regulates connexin (cx) 43 expression and function in astroglial cells from distinct brain regions. Reuss, B., Dermietzel, R., Unsicker, K. Glia (1998) [Pubmed]
  18. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury. Lee, I.H., Lindqvist, E., Kiehn, O., Widenfalk, J., Olson, L. J. Comp. Neurol. (2005) [Pubmed]
  19. Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP. Goldberg, G.S., Moreno, A.P., Lampe, P.D. J. Biol. Chem. (2002) [Pubmed]
  20. Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. Toyofuku, T., Yabuki, M., Otsu, K., Kuzuya, T., Hori, M., Tada, M. J. Biol. Chem. (1998) [Pubmed]
  21. Formation of heteromeric gap junction channels by connexins 40 and 43 in vascular smooth muscle cells. He, D.S., Jiang, J.X., Taffet, S.M., Burt, J.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  22. Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein. Ando, M., Katare, R.G., Kakinuma, Y., Zhang, D., Yamasaki, F., Muramoto, K., Sato, T. Circulation (2005) [Pubmed]
  23. Cellular expression of connexins in the rat brain: neuronal localization, effects of kainate-induced seizures and expression in apoptotic neuronal cells. Condorelli, D.F., Trovato-Salinaro, A., Mudò, G., Mirone, M.B., Belluardo, N. Eur. J. Neurosci. (2003) [Pubmed]
  24. Chronic effects of endothelin 1 and angiotensin II on gap junctions and intercellular communication in cardiac cells. Polontchouk, L., Ebelt, B., Jackels, M., Dhein, S. FASEB J. (2002) [Pubmed]
  25. Opposite regulation of connexin33 and connexin43 by LPS and IL-1alpha in spermatogenesis. Fiorini, C., Decrouy, X., Defamie, N., Segretain, D., Pointis, G. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  26. Autocrine regulation of myocyte Cx43 expression by VEGF. Pimentel, R.C., Yamada, K.A., Kléber, A.G., Saffitz, J.E. Circ. Res. (2002) [Pubmed]
  27. Proliferation-associated differences in the spatial and temporal expression of gap junction genes in rat liver. Neveu, M.J., Hully, J.R., Babcock, K.L., Vaughan, J., Hertzberg, E.L., Nicholson, B.J., Paul, D.L., Pitot, H.C. Hepatology (1995) [Pubmed]
  28. Immunogold evidence that neuronal gap junctions in adult rat brain and spinal cord contain connexin-36 but not connexin-32 or connexin-43. Rash, J.E., Staines, W.A., Yasumura, T., Patel, D., Furman, C.S., Stelmack, G.L., Nagy, J.I. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  29. Connexin-26 and connexin-43 are differentially expressed and regulated in the rat myometrium throughout late pregnancy and with the onset of labor. Orsino, A., Taylor, C.V., Lye, S.J. Endocrinology (1996) [Pubmed]
  30. Changes in gap-junction permeability, phosphorylation, and number mediated by phorbol ester and non-phorbol-ester tumor promoters in rat liver epithelial cells. Matesic, D.F., Rupp, H.L., Bonney, W.J., Ruch, R.J., Trosko, J.E. Mol. Carcinog. (1994) [Pubmed]
WikiGenes - Universities