Cited by 216Connexins and lens biologyIon channel regulation and functionNeuroscience and Neuropharmacology Research

Functional Expression of the Murine Connexin 36 Gene Coding for a Neuron-Specific Gap Junctional Protein

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Teubner, B., Degen, J., Söhl, G., Güldenagel, M., Bukauskas, F.F., Trexler, E.B., Verselis, V.K., De Zeeuw, C.I. +5 more·2000·The Journal of Membrane Biology

Abstract

The mouse connexin 36 (Cx36) gene was mapped on chromosome 2 and an identical transcriptional start site was determined in brain and retina on exon I. Rabbit polyclonal antibodies to the presumptive cytoplasmic loop of the Cx36 protein recognized in immunohistochemical analyses Cx36 expression in the retina, olfactory bulb, hippocampus, inferior olive and cerebellum. In olivary neurons strong punctate labeling at dendritic cell contacts and weaker labeling in the cytoplasm of dendrites were shown by immuno electron microscopy. After expression of mouse Cx36 cDNA in human HeLa cells, neurobiotin transfer was increased 1.8-fold and electrical conductance at least 15-fold compared to untransfected HeLa cells. No Lucifer Yellow transfer was detected in either untransfected or Cx36 transfected HeLa cells. Single Cx36 channels in transfected HeLa cells showed a unitary conductance of 14.3 + or - 0. 8 pS. The sensitivity of Cx36 channels to transjunctional voltage was low in both HeLa-Cx36 cells and Xenopus oocytes expressing mouse Cx36. No increased transfer of neurobiotin was detected in heterotypic gap junctions formed by Cx36 and 9 other connexins expressed in HeLa cells. Our results suggest that Cx36 channels function as electrical synapses for transmission of electrical and metabolic signals between neurons in the central nervous system.

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Research works printed but not linked: 41

  1. Adamson MC, Silver J, Kozak CA. The mouse homolog of the Gibbon ape leukemia virus receptor: genetic mapping and a possible receptor function in rodents. Virology. 1991;183:778–781. doi: 10.1016/0042-6822(91)91010-e. [DOI] [PubMed] [Google Scholar] · DOI
  2. Al-Ubaidi MR, White TW, Ripps H, Poras I, Avner P, Gomes D, Bruzzone R. Functional properties, developmental regulation, and chromosomal localization of murine connexin36, a gap-junctional protein expressed preferentially in retina and brain. J Neurosci Res. 2000;59:813–826. doi: 10.1002/(SICI)1097-4547(20000315)59:6<813::AID-JNR14>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar] · DOI
  3. Belluardo N, Trovato-Salinaro A, Mudo G, Hurd YL, Condorelli DF. Structure, chromosomal localization, and brain expression of human Cx36 gene. J Neurosci Res. 1999;57:740–752. [PubMed] [Google Scholar]
  4. Bittmann KS, LoTurco JJ. Differential regulation of connexin 26 and 43 in murine cortical precursors. Cerebral Cortex. 1999;9:188–195. doi: 10.1093/cercor/9.2.188. [DOI] [PubMed] [Google Scholar] · DOI
  5. Bruzzone R, White TW, Paul DL. Connections with con-nexins: the molecular basis of direct intercellular signaling. Eur J Biochem. 1996;238:1–27. doi: 10.1111/j.1432-1033.1996.0001q.x. [DOI] [PubMed] [Google Scholar] · DOI
  6. Condorelli DF, Parenti R, Spinella F, Trovato-Salinaro A, Belluardo N, Cardile V, Cicirata F. Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons. Eur J Neurosci. 1998;10:1202–1208. doi: 10.1046/j.1460-9568.1998.00163.x. [DOI] [PubMed] [Google Scholar] · DOI
  7. Dermietzel R, Traub O, Hwang TK, Beyer E, Bennett MVL, Spray DC, Willecke K. Differential expression of three gap junction proteins in developing and mature brain tissues. PNAS USA. 1989;86:10148–10152. doi: 10.1073/pnas.86.24.10148. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  8. Dermietzel R, Farooq M, Kessler JA, Althaus H, Hertzberg EL, Spray DC. Oligodendrocytes express gap junction proteins connexin32 and connexin45. Glia. 1997;20:101–114. [PubMed] [Google Scholar]
  9. De Zeeuw CI, Hertzberg EL, Mugnaini E. The dendritic lamellar body: a new neuronal organelle putatively associated with dendrodendritic gap junctions. J Neurosci. 1995;15:1587–1604. doi: 10.1523/JNEUROSCI.15-02-01587.1995. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  10. Draguhn A, Traub RD, Schmitz D, Jefferys JGR. Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature. 1998;394:189–192. doi: 10.1038/28184. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  11. Goldberg GS, Bechberger JF, Nauss CCG. A pre-loading method of evaluating gap junctional communication by fluorescent dye transfer. Biotechniques. 1995;18:490–497. [PubMed] [Google Scholar]
  12. Green EL. Genetics and Probability in Animal Breeding Experiments. Oxford University Press; New York: 1981. [Google Scholar]
  13. Hennemann H, Kozjek G, Dahl E, Nicholson BJ, Willecke K. Molecular cloning of mouse connexins26 and -32: similar genomic organization but distinct promoter sequences of two gap junction genes. Eur J Cell Biol. 1992;58:81–89. [PubMed] [Google Scholar]
  14. Horst M, Harth N, Hasilik A. Biosynthesis of glycosylated human lysozyme mutants. J Biol Chem. 1991;266:13914–13919. [PubMed] [Google Scholar]
  15. Kosaka T, Hama K. Gap junctions between non-pyramidal cell dendrites in the rat hippocampus (CA1 and CA3 regions): a combined Golgi-electron microscopy study. J Comp Neurol. 1985;231:150–161. doi: 10.1002/cne.902310203. [DOI] [PubMed] [Google Scholar] · DOI
  16. Kozak CA, Peyser M, Krall M, Mariano TM, Kumar CS, Pestka S, Mock BA. Molecular genetic markers spanning mouse chromosome 10. Genomics. 1990;8:519–524. doi: 10.1016/0888-7543(90)90039-w. [DOI] [PubMed] [Google Scholar] · DOI
  17. Kunzelmann P, Blümcke I, Traub O, Dermietzel R, Willecke K. Coexpression of connexin45 and -32 in oligodendrocytes of rat brain. J Neurocytol. 1997;26:17–22. doi: 10.1023/a:1018555207379. [DOI] [PubMed] [Google Scholar] · DOI
  18. Kunzelmann P, Schröder W, Traub O, Steinhäuser C, Dermietzel R, Willecke K. Late onset and increasing expression of the gap junction protein connexin30 in adult murine brain and long-term cultured astrocytes. Glia. 1999;25:111–119. doi: 10.1002/(sici)1098-1136(19990115)25:2<111::aid-glia2>3.0.co;2-i. [DOI] [PubMed] [Google Scholar] · DOI
  19. Lasater EM. Retinal horizontal cell gap junctional conductance is modulated by dopamine through a cyclic AMP-dependent protein kinase. PNAS USA. 1987;84:7319–7323. doi: 10.1073/pnas.84.20.7319. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  20. Mann-Metzer P, Yarom Y. Electrotonic coupling interacts with intrinsic properties to generate synchronized activity in cerebellar networks of inhibitory interneurons. J Neurosci. 1999;19:3298–306. doi: 10.1523/JNEUROSCI.19-09-03298.1999. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  21. Manthey D, Bukauskas FF, Lee CG, Kozak CA, Willecke K. Molecular cloning and functional expression of the mouse gap junction gene connexin-57 in human HeLa cells. J Biol Chem. 1999;274:14716–14723. doi: 10.1074/jbc.274.21.14716. [DOI] [PubMed] [Google Scholar] · DOI
  22. Nagy JI, Patel D, Ochalski PAY, Stelmack GL. Con-nexin30 in rodent, cat and human brain: Selective expression in gray matter astrocytes, colocalization with connexin43 at gap junctions and late developmental appearance. Neuroscience. 1999;88:447–468. doi: 10.1016/s0306-4522(98)00191-2. [DOI] [PubMed] [Google Scholar] · DOI
  23. Neuhaus IM, Dahl G, Werner R. Use of alternate promoters for tissue-specific expression of the gene coding for connexin32. Gene. 1995;158:257–262. doi: 10.1016/0378-1119(94)00899-4. [DOI] [PubMed] [Google Scholar] · DOI
  24. Neyton A, Trautmann A. Single-channel currents of an intercellular junction. Nature. 1985;317:331–335. doi: 10.1038/317331a0. [DOI] [PubMed] [Google Scholar] · DOI
  25. O'Brien J, Bruzzone R, White TW, Al-Ubaidi MR, Ripps H. Cloning and expression of two related connexins from the perch retina define a distinct subgroup of the connexin family. J Neurosci. 1998;18:7625–7637. doi: 10.1523/JNEUROSCI.18-19-07625.1998. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  26. Rise ML, Frankel WN, Coffin JM, Seyfried TN. Genes for epilepsy mapped in the mouse. Science. 1991;253:669–673. doi: 10.1126/science.1871601. [DOI] [PubMed] [Google Scholar] · DOI
  27. Rubin JB, Verselis VK, Bennett MV, Bargiello TA. Molecular analysis of voltage dependence of heterotypic gap junctions formed by connexins 26 and 32. Biophys J. 1992;62:183–193. doi: 10.1016/S0006-3495(92)81804-0. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  28. Saez JC, Martinez AD, Branes MC, Gonzalez HE. Regulation of gap junctions by protein phosphorylation. Braz J Med Biol Res. 1998;31:593–600. doi: 10.1590/s0100-879x1998000500001. [DOI] [PubMed] [Google Scholar] · DOI
  29. Schmalbruch H, Jahnsen H. Gap junctions on CA3 pyramidal cells of guinea pig hippocampus shown by freeze-fracture. Brain Res. 1981;217:175–178. doi: 10.1016/0006-8993(81)90196-7. [DOI] [PubMed] [Google Scholar] · DOI
  30. Shiosaka S, Yamamoto T, Hertzberg EL, Nagy JI. Gap junction protein in rat hippocampus: correlative light and electron microscope immunohistochemical localization. J Comp Neurol. 1989;281:282–297. doi: 10.1002/cne.902810210. [DOI] [PubMed] [Google Scholar] · DOI
  31. Simon AM, Goodenough DA. Diverse functions of vertebrate gap junctions. Trends Cell Biol. 1998;8:477–483. doi: 10.1016/s0962-8924(98)01372-5. [DOI] [PubMed] [Google Scholar] · DOI
  32. Söhl G, Gillen C, Bosse F, Gleichmann M, Müller HW, Willecke K. A second alternative transcript of the gap junction gene connexin32 is expressed in murine Schwann cells and modulated in injured sciatic nerve. Eur J Cell Biol. 1996;69:267–75. [PubMed] [Google Scholar]
  33. Söhl G, Degen J, Teubner B, Willecke K. The murine gap junction gene connexin36 is highly expressed in mouse retina and regulated during brain development. FEBS Lett. 1998;428:27–31. doi: 10.1016/s0014-5793(98)00479-7. [DOI] [PubMed] [Google Scholar] · DOI
  34. Spray DC, Dermietzel R. Gap Junctions in the Nervous System. Springer; New York: 1996. pp. 1–311. [Google Scholar]
  35. Srinivas M, Rozental R, Kojima T, Dermietzel R, Mehler M, Condorelli DF, Kessler JA, Spray DC. Functional properties of channels formed by the neuronal gap junction protein Connexin36. J Neurosci. 1999;19:9848–9855. doi: 10.1523/JNEUROSCI.19-22-09848.1999. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  36. Strata F, Atzori M, Molnar M, Ugolini G, Tempia F, Cherubini E. A pacemaker current in dye-coupled hilar interneurones contributes to the generation of giant GABAergic potentials in developing hippocampus. J Neurosci. 1997;17:1435–1446. doi: 10.1523/JNEUROSCI.17-04-01435.1997. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  37. Vaney DJ. Patterns of neuronal coupling in the retina. Prog Ret Eye Res. 1994;13:301–355. [Google Scholar]
  38. Verselis VK, Ginter CS, Bargiello TA. Opposite voltage gating polarities of two closely related connexins. Nature. 1994;368:348–51. doi: 10.1038/368348a0. [DOI] [PubMed] [Google Scholar] · DOI
  39. White TW, Deans MR, O'Brien J, Al-Ubaidi MR, Goodenough DA, Ripps H, Bruzzone R. Functional characteristics of skate connexin35, a member of the gamma subfamily of connexins expressed in the vertebrate retina. Eur J Neurosci. 1999;11:1883–1890. doi: 10.1046/j.1460-9568.1999.00607.x. [DOI] [PubMed] [Google Scholar] · DOI
  40. Wilders R, Jongsma HJ. Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels. Biophys J. 1992;63:942–953. doi: 10.1016/S0006-3495(92)81664-8. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  41. Yamamoto T, Ochalski A, Hertzberg EL, Nagy JI. LM and EM immunolocalization of the gap junctional protein connexin 43 in rat brain. Brain Res. 1990;508:313–319. doi: 10.1016/0006-8993(90)90415-8. [DOI] [PubMed] [Google Scholar] · DOI

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Authors
Teubner, B., Degen, J., Söhl, G., Güldenagel, M., Bukauskas, F. F., Trexler, E. B., Verselis, V. K., De Zeeuw, C. I., Lee, C. G., Kozak, C. A., Petrasch-Parwez, E., Dermietzel, R., & Willecke, K.
Affiliations
  • University of Bonn (DE)
  • Albert Einstein College of Medicine (US)
  • National Institutes of Health (US)
  • Ruhr University Bochum (DE)
Venue
The Journal of Membrane Biology
Published
2000-08
Volume
176
Issue
3
Pages
249-262
ISSN
0022-2631 (ISSN-L)
OpenAlex
W2005655563
Cited by
216
References
0
Citations by year
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FWCI
3.97
Type
journal article
Language
en
Open access
Locations
  • The Journal of Membrane Biology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (SFB400)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS367060, R01NS036706)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
connexin 36, gap junctions, electrical synapses, HeLa cells, Xenopus oocytes, heterotypic gap junctions, inferior olive, retina, olfactory bulb, hippocampus, cerebellum, chromosome 2
MeSH terms
Gap Junction delta-2 Protein, Animals, Antibody Specificity, Base Sequence, Biotin, Brain, Carbon Dioxide, Chromosome Mapping, Crosses, Genetic, Electrophysiology, Eye Proteins, Fluorescent Dyes, Genes, HeLa Cells, Humans, Isoquinolines, Membrane Potentials, Mice, Inbred C57BL, Molecular Sequence Data, Muridae, Nerve Tissue Proteins, Neurons, Oocytes, Rabbits, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Retina, Transcription, Genetic, Transfection, Xenopus laevis, Ion Channel Gating, Arachidonic Acid, Gap Junctions, Connexins, Mice

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