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Gene Review

Gjd2  -  gap junction protein, delta 2

Mus musculus

Synonyms: Connexin-36, Cx36, Gap junction alpha-9 protein, Gap junction delta-2 protein, Gja9, ...
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Disease relevance of Gja9


High impact information on Gja9


Chemical compound and disease context of Gja9

  • Suppression was achieved by intravitreal injections of GABA, TTX, or in Cx36 KO animals by crushing the optic nerve and waiting for ganglion cells to degenerate [7].

Biological context of Gja9

  • Replacement by a lacZ reporter gene assigns mouse connexin36, 45 and 43 to distinct cell types in pancreatic islets [8].
  • The second aim was to determine whether prolonged dark adaptation affects protein expression of two important Cx in retina: neuronal Cx36 and glial Cx43 [9].
  • In conclusion, we observed a distinct temporal expression pattern for Cx36, Cx43, and Cx45, which is probably related to particular roles in retinal function and maintenance of homeostasis during development of the mouse retina [10].
  • The present study was undertaken to determine the distribution pattern of Cx36, Cx43, and Cx45 by immunofluorescence, as well as their gene expression levels by quantitative PCR during postnatal development of the mouse retina [10].
  • Terminal neuronal differentiation is heralded by the expression of more advanced neurofilament proteins, increased morphologic maturation, the elaboration of inward currents and action potentials that possess mature physiological properties, and changing profiles of expression of connexin subtypes, including upregulation of Cx36 expression [11].

Anatomical context of Gja9

  • Moreover, we have located cx36 puncta at the axonal terminals of BPGus-GFP cells, and we have found that these BPGus-GFP-associated cx36 puncta always colocalized with AII amacrine cell processes [12].
  • Critical role of the transcriptional repressor neuron-restrictive silencer factor in the specific control of connexin36 in insulin-producing cell lines [13].
  • Among the 20 members in the connexin family of gap junction proteins, only connexin36 (Cx36) is firmly established to be expressed in neurons and to form electrical synapses at widely distributed interneuronal gap junctions in mammalian brain [14].
  • Cx36 from mouse brain and Cx36-transfected HeLa cells was found to coimmunoprecipitate with ZO-1 [14].
  • High-resolution proteomic mapping in the vertebrate central nervous system: close proximity of connexin35 to NMDA glutamate receptor clusters and co-localization of connexin36 with immunoreactivity for zonula occludens protein-1 (ZO-1) [15].

Associations of Gja9 with chemical compounds

  • Since connexin36 expression levels change after seizures, we examined the expression of both pannexin1 and connexin36 in cerebral cortex, hippocampus, cerebellum and brain stem at different time intervals (2, 4 and 8 h) after i.p. injection of 4-aminopyridine, which resulted in systemic seizures [2].
  • During glucose stimulation, islets of Cx36(-/-) mice did not display the regular oscillations of intracellular calcium concentrations ([Ca(2+)](i)) seen in controls due to the loss of cell-to-cell synchronization of [Ca(2+)](i) changes [16].
  • In contrast, expression of the connexin36 gene was inducible by TSA or DP-REST:ER only in pancreatic alpha and beta cells, but not in neuronal and pituitary cells, indicating that transcriptional repression by REST functions in a cell type-specific manner [17].
  • In view of the prominent role of cytosolic Ca(2+) in this secretion, we have monitored this cation, and have found that its handling is altered in populations of insulin-producing cells lacking Cx36 [18].
  • We have recently shown that pharmacological gap junction blockade abolishes kainate-induced gamma oscillations in connexin36 knockout mice; without such gap junction blockade, gamma oscillations do occur in the knockout mice, albeit at reduced power compared with wild-type mice [6].
  • Taken together, these data demonstrate that chronic exposure to palmitate inhibits the Cx36 expression through PKA-mediated ICER-1gamma overexpression [19].

Physical interactions of Gja9

  • Binding competition experiments with synthetic peptides mapped the calmodulin binding site to a 10-30 amino acid segment at the beginning of the C-terminal domain of Cx36 [20].

Regulatory relationships of Gja9

  • Cx26 immunofluorescence and a beta-gal reporter under regulatory control of the Cx36 promoter did not colocalize with a horizontal cell marker, indicating that these genes are not expressed by horizontal cells [21].
  • Furthermore we examined connexin 36 expressing cells in the mouse olfactory bulb by analyzing transgenic mice in which the connexin 36 coding sequence was replaced with histological reporters [22].

Other interactions of Gja9

  • Transcripts of three connexin isoforms (Cx36, Cx43 and Cx45) have been reported in rodent pancreatic islets, but the precise distribution of the cognate proteins is still unknown [8].
  • Based on the presence of sequence corresponding to a putative PDZ binding motif in Cx36, we investigated anatomical relationships and molecular association of Cx36 with ZO-1 [14].
  • The finding of increase in connexin protein without increase in mRNA suggests regulation of Cx32 and Cx36 expression at the translational or post-translational level [1].
  • Microscopy was used to further examine the distribution of Cx26 and Cx36 [21].
  • The increase in Cx32 and Cx36 expression was intense and specific to parvalbumin-positive inhibitory interneurons of CA1, as assessed by double immunofluorescence [1].

Analytical, diagnostic and therapeutic context of Gja9


  1. Global ischemia-induced increases in the gap junctional proteins connexin 32 (Cx32) and Cx36 in hippocampus and enhanced vulnerability of Cx32 knock-out mice. Oguro, K., Jover, T., Tanaka, H., Lin, Y., Kojima, T., Oguro, N., Grooms, S.Y., Bennett, M.V., Zukin, R.S. J. Neurosci. (2001) [Pubmed]
  2. Expression of pannexin1 in the CNS of adult mouse: cellular localization and effect of 4-aminopyridine-induced seizures. Zappalà, A., Cicero, D., Serapide, M.F., Paz, C., Catania, M.V., Falchi, M., Parenti, R., Pantò, M.R., La Delia, F., Cicirata, F. Neuroscience (2006) [Pubmed]
  3. Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina. Deans, M.R., Volgyi, B., Goodenough, D.A., Bloomfield, S.A., Paul, D.L. Neuron (2002) [Pubmed]
  4. Connexin36 mediates spike synchrony in olfactory bulb glomeruli. Christie, J.M., Bark, C., Hormuzdi, S.G., Helbig, I., Monyer, H., Westbrook, G.L. Neuron (2005) [Pubmed]
  5. Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Deans, M.R., Gibson, J.R., Sellitto, C., Connors, B.W., Paul, D.L. Neuron (2001) [Pubmed]
  6. Contrasting roles of axonal (pyramidal cell) and dendritic (interneuron) electrical coupling in the generation of neuronal network oscillations. Traub, R.D., Pais, I., Bibbig, A., LeBeau, F.E., Buhl, E.H., Hormuzdi, S.G., Monyer, H., Whittington, M.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. In vivo studies of signaling in rod pathways of the mouse using the electroretinogram. Robson, J.G., Maeda, H., Saszik, S.M., Frishman, L.J. Vision Res. (2004) [Pubmed]
  8. Replacement by a lacZ reporter gene assigns mouse connexin36, 45 and 43 to distinct cell types in pancreatic islets. Theis, M., Mas, C., Döring, B., Degen, J., Brink, C., Caille, D., Charollais, A., Krüger, O., Plum, A., Nepote, V., Herrera, P., Meda, P., Willecke, K. Exp. Cell Res. (2004) [Pubmed]
  9. Prolonged dark adaptation changes connexin expression in the mouse retina. Kihara, A.H., Mantovani de Castro, L., Moriscot, A.S., Hamassaki, D.E. J. Neurosci. Res. (2006) [Pubmed]
  10. Expression of connexins 36, 43, and 45 during postnatal development of the mouse retina. Kihara, A.H., Mantovani de Castro, L., Belmonte, M.A., Yan, C.Y., Moriscot, A.S., Hamassaki, D.E. J. Neurobiol. (2006) [Pubmed]
  11. Temporal expression of neuronal connexins during hippocampal ontogeny. Rozental, R., Srinivas, M., Gökhan, S., Urban, M., Dermietzel, R., Kessler, J.A., Spray, D.C., Mehler, M.F. Brain Res. Brain Res. Rev. (2000) [Pubmed]
  12. Electrical synapses in retinal ON cone bipolar cells: subtype-specific expression of connexins. Han, Y., Massey, S.C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Critical role of the transcriptional repressor neuron-restrictive silencer factor in the specific control of connexin36 in insulin-producing cell lines. Martin, D., Tawadros, T., Meylan, L., Abderrahmani, A., Condorelli, D.F., Waeber, G., Haefliger, J.A. J. Biol. Chem. (2003) [Pubmed]
  14. Neuronal connexin36 association with zonula occludens-1 protein (ZO-1) in mouse brain and interaction with the first PDZ domain of ZO-1. Li, X., Olson, C., Lu, S., Kamasawa, N., Yasumura, T., Rash, J.E., Nagy, J.I. Eur. J. Neurosci. (2004) [Pubmed]
  15. High-resolution proteomic mapping in the vertebrate central nervous system: close proximity of connexin35 to NMDA glutamate receptor clusters and co-localization of connexin36 with immunoreactivity for zonula occludens protein-1 (ZO-1). Rash, J.E., Pereda, A., Kamasawa, N., Furman, C.S., Yasumura, T., Davidson, K.G., Dudek, F.E., Olson, C., Li, X., Nagy, J.I. J. Neurocytol. (2004) [Pubmed]
  16. Loss of connexin36 channels alters beta-cell coupling, islet synchronization of glucose-induced Ca2+ and insulin oscillations, and basal insulin release. Ravier, M.A., Güldenagel, M., Charollais, A., Gjinovci, A., Caille, D., Söhl, G., Wollheim, C.B., Willecke, K., Henquin, J.C., Meda, P. Diabetes (2005) [Pubmed]
  17. Cell type-specific regulation of RE-1 silencing transcription factor (REST) target genes. Hohl, M., Thiel, G. Eur. J. Neurosci. (2005) [Pubmed]
  18. Cx36 involvement in insulin secretion: characteristics and mechanism. Meda, P. Cell Commun. Adhes. (2003) [Pubmed]
  19. ICER-1gamma overexpression drives palmitate-mediated connexin36 down-regulation in insulin-secreting cells. Allagnat, F., Alonso, F., Martin, D., Abderrahmani, A., Waeber, G., Haefliger, J.A. J. Biol. Chem. (2008) [Pubmed]
  20. Calcium-dependent binding of calmodulin to neuronal gap junction proteins. Burr, G.S., Mitchell, C.K., Keflemariam, Y.J., Heidelberger, R., O'Brien, J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  21. Mouse horizontal cells do not express connexin26 or connexin36. Deans, M.R., Paul, D.L. Cell Commun. Adhes. (2001) [Pubmed]
  22. Neuronal gap junctions in the mouse main olfactory bulb: morphological analyses on transgenic mice. Kosaka, T., Deans, M.R., Paul, D.L., Kosaka, K. Neuroscience (2005) [Pubmed]
  23. Different functional types of bipolar cells use different gap-junctional proteins. Lin, B., Jakobs, T.C., Masland, R.H. J. Neurosci. (2005) [Pubmed]
  24. Loss of connexin36 increases retinal cell vulnerability to secondary cell loss. Striedinger, K., Petrasch-Parwez, E., Zoidl, G., Napirei, M., Meier, C., Eysel, U.T., Dermietzel, R. Eur. J. Neurosci. (2005) [Pubmed]
  25. Fine structural localization of connexin-36 immunoreactivity in mouse cerebral cortex and thalamus. Liu, X.B., Jones, E.G. J. Comp. Neurol. (2003) [Pubmed]
  26. Short-range functional interaction between connexin35 and neighboring chemical synapses. Pereda, A., O'Brien, J., Nagy, J.I., Smith, M., Bukauskas, F., Davidson, K.G., Kamasawa, N., Yasumura, T., Rash, J.E. Cell Commun. Adhes. (2003) [Pubmed]
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