Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-29T02:42:32.692Z Has data issue: false hasContentIssue false

Expression and modulation of connexin30.2, a novel gap junction protein in the mouse retina

Published online by Cambridge University Press:  11 June 2010

LUIS PÉREZ DE SEVILLA MÜLLER
Affiliation:
Department of Neurobiology, University of Oldenburg, Oldenburg, Germany
KARIN DEDEK
Affiliation:
Department of Neurobiology, University of Oldenburg, Oldenburg, Germany
ULRIKE JANSSEN-BIENHOLD
Affiliation:
Department of Neurobiology, University of Oldenburg, Oldenburg, Germany
ARNDT MEYER
Affiliation:
Department of Neurobiology, University of Oldenburg, Oldenburg, Germany
MARIA M. KREUZBERG
Affiliation:
Institute for Genetics, University of Bonn, Bonn, Germany
SUSANNE LORENZ
Affiliation:
Department of Neurobiology, University of Oldenburg, Oldenburg, Germany
KLAUS WILLECKE
Affiliation:
Institute for Genetics, University of Bonn, Bonn, Germany
RETO WEILER*
Affiliation:
Department of Neurobiology, University of Oldenburg, Oldenburg, Germany
*
Address correspondence and reprint requests to: Professor Reto Weiler, Department of Neurobiology, University of Oldenburg, P.O. Box 2503, D-26111 Oldenburg, Germany. E-mail: [email protected]

Abstract

Mammalian retinae express multiple connexins that mediate the metabolic and electrical coupling of various cell types. In retinal neurons, only connexin36, connexin45, connexin50, and connexin57 have been described so far. Here, we present an analysis of a novel retinal connexin, connexin30.2 (Cx30.2), and its regulation in the mouse retina. To analyze the expression of Cx30.2, we used a transgenic mouse line in which the coding region of Cx30.2 was replaced by lacZ reporter DNA. We detected the lacZ signal in the nuclei of neurons located in the inner nuclear layer and the ganglion cell layer (GCL). In this study, we focused on the GCL and characterized the morphology of the Cx30.2-expressing cells. Using immunocytochemistry and intracellular dye injections, we found six different types of Cx30.2-expressing ganglion cells: one type of ON-OFF, three types of OFF, and two types of ON ganglion cells; among the latter was the RGA1 type. We show that RGA1 cells were heterologously coupled to numerous displaced amacrine cells. Our results suggest that these gap junction channels may be heterotypic, involving Cx30.2 and a connexin yet unidentified in the mouse retina. Gap junction coupling can be modulated by protein kinases, a process that plays a major role in retinal adaptation. Therefore, we studied the protein kinase–induced modulation of coupling between RGA1 and displaced amacrine cells. Our data provide evidence that coupling of RGA1 cells to displaced amacrine cells is mediated by Cx30.2 and that the extent of this coupling is modulated by protein kinase C.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Badea, T.D. & Nathans, J. (2004). Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter. The Journal of Comparative Neurology 480, 331351.CrossRefGoogle ScholarPubMed
Bao, X., Altenberg, G.A. & Reuss, L. (2004). Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation. American Journal of Physiology—Cell Physiology 286, C647C654.CrossRefGoogle Scholar
Bloomfield, S.A. & Völgyi, B. (2009). The diverse functional roles and regulation of neuronal gap junctions in the retina. Nature Reviews Neuroscience 10, 495506.CrossRefGoogle ScholarPubMed
Bukauskas, F.F., Angele, A.B., Verselis, V.K. & Bennett, M.V. (2002). Coupling asymmetry of heterotypic connexin 45/connexin 43-EGFP gap junctions: properties of fast and slow gating mechanisms. Proceedings of the National Academy of Sciences of the United States of America 99, 71137118.CrossRefGoogle ScholarPubMed
Bukauskas, F.F., Kreuzberg, M.M., Rackauskas, M., Bukauskiene, A., Bennett, M.V., Verselis, V.K. & Willecke, K. (2006). Properties of mouse connexin 30.2 and human connexin 31.9 hemichannels: Implications for atrioventricular conduction in the heart. Proceedings of the National Academy of Sciences of the United States of America 103, 97269731.CrossRefGoogle ScholarPubMed
Bunt, A.H. (1976). Ramification patterns of ganglion cells dendrites in the retina of the albino rat. Brain Research 103, 18.CrossRefGoogle ScholarPubMed
Coombs, J., van der List, D., Wang, G.Y. & Chalupa, L.M. (2006). Morphological properties of mouse retinal ganglion cells. Neuroscience 140, 123136.CrossRefGoogle ScholarPubMed
Deans, M.R., Volgyi, B., Goodenough, D.A., Bloomfield, S.A. & Paul, D.L. (2002). Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina. Neuron 36, 703712.CrossRefGoogle ScholarPubMed
Dedek, K., Breuninger, T., Pérez de Sevilla Müller, L., Maxeiner, S., Schultz, K., Janssen-Bienhold, U., Willecke, K., Euler, T. & Weiler, R. (2009). A novel type of interplexiform amacrine cell in the mouse retina. European Journal of Neuroscience 30, 217228.CrossRefGoogle ScholarPubMed
Dedek, K., Schultz, K., Pieper, M., Dirks, P., Maxeiner, S., Willecke, K., Weiler, R. & Janssen-Bienhold, U. (2006). Localization of heterotypic gap junctions composed of connexin45 and connexin36 in the rod pathway of the mouse retina. European Journal of Neuroscience 24, 16751686.CrossRefGoogle ScholarPubMed
Feigenspan, A., Janssen-Bienhold, U., Hormuzdi, S., Monyer, H., Degen, J., Söhl, G., Willecke, K., Ammermüller, J. & Weiler, R. (2004). Expression of connexin36 in cone pedicles and OFF-cone bipolar cells of the mouse retina. The Journal of Neuroscience 24, 33253334.CrossRefGoogle ScholarPubMed
Feigenspan, A., Teubner, B., Willecke, K. & Weiler, R. (2001). Expression of neuronal connexin36 in AII amacrine cells of the mammalian retina. The Journal of Neuroscience 21, 230239.CrossRefGoogle ScholarPubMed
Güldenagel, M., Ammermüller, J., Feigenspan, A., Teubner, B., Degen, J., Söhl, G., Willecke, K. & Weiler, R. (2001). Visual transmission deficits in mice with targeted disruption of the gap junction gene connexin36. The Journal of Neuroscience 21, 60366044.CrossRefGoogle ScholarPubMed
Hampson, E.C., Vaney, D.I. & Weiler, R. (1992). Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina. The Journal of Neuroscience 12, 49114922.CrossRefGoogle ScholarPubMed
Han, Y. & Massey, S.C. (2005). Electrical synapses in retinal ON cone bipolar cells: Subtype-specific expression of connexins. Proceedings of the National Academy of Sciences of the United States of America 102, 1331313318.CrossRefGoogle ScholarPubMed
He, S., Weiler, R. & Vaney, D.I. (2000). Endogenous dopaminergic regulation of horizontal cell coupling in the mammalian retina. The Journal of Comparative Neurology 418, 3340.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Hidaka, S., Akahori, Y. & Kurosawa, Y. (2004). Dendrodendritic electrical synapses between mammalian retinal ganglion cells. The Journal of Neuroscience 24, 1055310567.CrossRefGoogle ScholarPubMed
Hidaka, S., Kato, T. & Miyachi, E. (2002). Expression of gap junction connexin36 in adult rat retinal ganglion cells. The Journal of Integrative Neuroscience 1, 322.CrossRefGoogle ScholarPubMed
Hombach, S., Janssen-Bienhold, U., Söhl, G., Schubert, T., Büssow, H., Ott, T., Weiler, R. & Willecke, K. (2004). Functional expression of connexin57 in horizontal cells of the mouse retina. European Journal of Neuroscience 19, 26332640.CrossRefGoogle ScholarPubMed
Huxlin, K.R. & Goodchild, A.K. (1997). Retinal ganglion cells in the albino rat: Revised morphological classification. The Journal of Comparative Neurology 385, 309323.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Janssen-Bienhold, U., Trümpler, J., Hilgen, G., Schultz, K., Pérez de Sevilla Müller, L., Sonntag, S., Dedek, K., Dirks, P., Willecke, K. & Weiler, R. (2009). Connexin57 is expressed in dendro-dendritic and axo-axonal gap junctions of mouse horizontal cells and its distribution is modulated by light. Journal of Comparative Neurology 513, 363374.CrossRefGoogle ScholarPubMed
Jeon, C.J., Strettoi, E. & Masland, R.H. (1998). The major cell populations of the mouse retina. The Journal of Neuroscience 18, 89368946.CrossRefGoogle ScholarPubMed
Kao, Y.H. & Sterling, P. (2006). Displaced GAD65 amacrine cells of the guinea pig retina are morphologically diverse. Visual Neuroscience 23, 931939.CrossRefGoogle ScholarPubMed
Kihara, A.H., de Castro, L.M., Moriscot, A.S. & Hamassaki, D.E. (2006). Prolonged dark adaptation changes connexin expression in the mouse retina. Journal of Neuroscience Research 83, 13311341.CrossRefGoogle ScholarPubMed
Kirchhoff, S., Nelles, E., Hagendorff, A., Krüger, O., Traub, O. & Willecke, K. (1998). Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice. Current Biology 8, 299302.CrossRefGoogle ScholarPubMed
Kong, J.H., Fish, D.R., Rockhill, R.L. & Masland, R.H. (2005). Diversity of ganglion cells in the mouse retina: Unsupervised morphological classification and its limits. The Journal of Comparative Neurology 489, 293310.CrossRefGoogle ScholarPubMed
Kreuzberg, M.M., Deuchars, J., Weiss, E., Schober, A., Sonntag, S., Wellershaus, K., Draguhn, A. & Willecke, K. (2008). Expression of connexin30.2 in interneurons of the central nervous system in the mouse. Molecular and Cellular Neuroscience 37, 119134.CrossRefGoogle ScholarPubMed
Kreuzberg, M.M., Schrickel, J.W., Ghanem, A., Kim, J.S., Degen, J., Janssen-Bienhold, U., Lewalter, T., Tiemann, K. & Willecke, K. (2006). Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node. Proceedings of the National Academy of Sciences of the United States of America 103, 59595964.CrossRefGoogle ScholarPubMed
Kreuzberg, M.M., Söhl, G., Kim, J.S., Verselis, V.K., Willecke, K. & Bukauskas, F.F. (2005). Functional properties of mouse connexin30.2 expressed in the conduction system of the heart. Circulation Research 96, 11691177.CrossRefGoogle ScholarPubMed
Lee, E.J., Han, J.W., Kim, H.J., Kim, I.B., Lee, M.Y., Oh, S.J., Chung, J.W. & Chun, M.H. (2003). The immunocytochemical localization of connexin 36 at rod and cone gap junctions in the guinea pig retina. European Journal of Neuroscience 18, 29252934.CrossRefGoogle ScholarPubMed
Li, X., Kamasawa, N., Ciolofan, C., Olson, C.O., Lu, S., Davidson, K.G., Yasumura, T., Shigemoto, R., Rash, J.E. & Nagy, J.I. (2008). Connexin45-containing neuronal gap junctions in rodent retina also contain connexin36 in both apposing hemiplaques, forming bihomotypic gap junctions, with scaffolding contributed by zonula occludens-1. The Journal of Neuroscience 28, 97699789.CrossRefGoogle ScholarPubMed
Lin, B., Jakobs, T.C. & Masland, R.H. (2005). Different functional types of bipolar cells use different gap-junctional proteins. The Journal of Neuroscience 25, 66966701.CrossRefGoogle ScholarPubMed
Lin, B. & Masland, R.H. (2006). Populations of wide-field amacrine cells in the mouse retina. The Journal of Comparative Neurology 499, 797809.CrossRefGoogle ScholarPubMed
Matesic, D., Tillen, T. & Sitaramayya, A. (2003). Cx40 expression in bovine and rat retinae. Cell Biology International 27, 8999.CrossRefGoogle Scholar
Maxeiner, S., Dedek, K., Janssen-Bienhold, U., Ammermüller, J., Brune, H., Kirsch, T., Pieper, M., Degen, J., Krüger, O., Willecke, K. & Weiler, R. (2005). Deletion of connexin45 in mouse retinal neurons disrupts the rod/cone signaling pathway between AII amacrine and ON cone bipolar cells and leads to impaired visual transmission. The Journal of Neuroscience 25, 566576.CrossRefGoogle ScholarPubMed
Mills, S.L., O’Brien, J.J., Li, W., O’Brien, J. & Massey, S.C. (2001). Rod pathways in the mammalian retina use connexin 36. The Journal of Comparative Neurology 436, 336350.CrossRefGoogle ScholarPubMed
Moreno, A.P. & Lau, A.F. (2007). Gap junction channel gating modulated through protein phosphorylation. Progress in Biophysics and Molecular Biology 94, 107119.CrossRefGoogle ScholarPubMed
Nirenberg, S. & Cepko, C. (1993). Targeted ablation of diverse cell classes in the nervous system in vivo. The Journal of Neuroscience 13, 32383251.CrossRefGoogle ScholarPubMed
Nirenberg, S. & Meister, M. (1997). The light response of retinal ganglion cells is truncated by a displaced amacrine circuit. Neuron 18, 637650.CrossRefGoogle ScholarPubMed
O’Brien, J.J., Li, W., Pan, F., Keung, J., O’Brien, J. & Massey, S.C. (2006). Coupling between A-type horizontal cells is mediated by connexin 50 gap junctions in the rabbit retina. The Journal of Neuroscience 26, 1162411636.CrossRefGoogle ScholarPubMed
Pan, F., Paul, D.L., Bloomfield, S.A. & Völgyi, B. (2010). Connexin36 is required for gap junctional coupling of most ganglion cell subtypes in the mouse retina. The Journal of Comparative Neurology 518, 911927.CrossRefGoogle ScholarPubMed
Pérez de Sevilla Müller, L., Shelley, J. & Weiler, R. (2007). Displaced amacrine cells of the mouse retina. The Journal of Comparative Neurology 505, 177189.CrossRefGoogle ScholarPubMed
Rackauskas, M., Verselis, V.K. & Bukauskas, F.F. (2007). Permeability of homotypic and heterotypic gap junction channels formed of cardiac connexins mCx30.2, Cx40, Cx43, and Cx45. American Journal of Physiology. Heart and Circulatory Physiology 293, H1729H1736.CrossRefGoogle ScholarPubMed
Schubert, T., Degen, J., Willecke, K., Hormuzdi, S.G., Monyer, H. & Weiler, R. (2005 a). Connexin36 mediates gap junctional coupling of alpha-ganglion cells in mouse retina. The Journal of Comparative Neurology 485, 191201.CrossRefGoogle ScholarPubMed
Schubert, T., Maxeiner, S., Kruger, O., Willecke, K. & Weiler, R. (2005 b). Connexin45 mediates gap junctional coupling of bistratified ganglion cells in the mouse retina. The Journal of Comparative Neurology 490, 2939.CrossRefGoogle ScholarPubMed
Shelley, J., Dedek, K., Schubert, T., Feigenspan, A., Schultz, K., Hombach, S., Willecke, K. & Weiler, R. (2006). Horizontal cell receptive fields are reduced in connexin57-deficient mice. European Journal of Neuroscience 23, 31763186.CrossRefGoogle ScholarPubMed
Simon, A.M. & McWhorter, A.R. (2003). Decreased intercellular dye-transfer and downregulation of non-ablated connexins in aortic endothelium deficient in connexin37 or connexin40. Journal of Cell Science 116, 22232236.CrossRefGoogle ScholarPubMed
Söhl, G., Degen, J., Teubner, B. & Willecke, K. (1998). The murine gap junction gene connexin36 is highly expressed in mouse retina and regulated during brain development. FEBS Letters 428, 2731.CrossRefGoogle ScholarPubMed
Söhl, G., Maxeiner, S. & Willecke, K. (2005). Expression and functions of neuronal gap junctions. Nature Reviews Neuroscience 6, 191200.CrossRefGoogle ScholarPubMed
Spray, D.C., Ye, Z.C. & Ransom, B.R. (2006) Functional connexin “hemichannels”: a critical appraisal. Glia 54, 758773.CrossRefGoogle ScholarPubMed
Sun, W., Li, N. & He, S. (2002 a). Large-scale morphological survey of mouse retinal ganglion cells. The Journal of Comparative Neurology 451, 115126.CrossRefGoogle ScholarPubMed
Sun, W., Li, N. & He, S. (2002 b). Large-scale morphological survey of rat retinal ganglion cells. Visual Neuroscience 19, 483493.CrossRefGoogle ScholarPubMed
Urschel, S., Höher, T., Schubert, T., Alev, C., Söhl, G., Wörsdörfer, P., Asahara, T., Dermietzel, R., Weiler, R. & Willecke, K. (2006). Protein kinase A-mediated phosphorylation of connexin36 in mouse retina results in decreased gap junctional communication between AII amacrine cells. Journal of Biological Chemistry 281, 3316333171.CrossRefGoogle ScholarPubMed
Vaney, D.I. (1991). Many diverse types of retinal neurons show tracer coupling when injected with biocytin or Neurobiotin. Neuroscience Letters 125, 187190.CrossRefGoogle ScholarPubMed
Völgyi, B., Abrams, J., Paul, D.L. & Bloomfield, S.A. (2005). Morphology and tracer coupling pattern of alpha ganglion cells in the mouse retina. The Journal of Comparative Neurology 492, 6677.CrossRefGoogle ScholarPubMed
Völgyi, B., Cheda, S. & Bloomfield, S.A. (2009). Tracer coupling patterns of the ganglion cell subtypes in the mouse retina. The Journal of Comparative Neurology 512, 664687.CrossRefGoogle ScholarPubMed
Weiler, R., Pottek, M., He, S. & Vaney, D.I. (2000). Modulation of coupling between retinal horizontal cells by retinoic acid and endogenous dopamine. Brain Research Reviews 32, 121129.CrossRefGoogle ScholarPubMed
Weng, S., Sun, W. & He, S. (2005). Identification of ON-OFF direction-selective ganglion cells in the mouse retina. The Journal of Physiology 562, 915923.CrossRefGoogle ScholarPubMed
Wright, L.L. & Vaney, D.I. (2000). The fountain amacrine cells of the rabbit retina. Visual Neuroscience 17, 11451156.CrossRefGoogle ScholarPubMed
Wright, L.L. & Vaney, D.I. (2004). The type 1 polyaxonal amacrine cells of the rabbit retina: a tracer-coupling study. Visual Neuroscience 21, 145155.CrossRefGoogle ScholarPubMed
Xia, X.B. & Mills, S.L. (2004). Gap junctional regulatory mechanisms in the AII amacrine cell of the rabbit retina. Visual Neuroscience 21, 791805.CrossRefGoogle ScholarPubMed
Xin, D. & Bloomfield, S.A. (1997). Tracer coupling pattern of amacrine and ganglion cells in the rabbit retina. The Journal of Comparative Neurology 383, 512528.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Supplementary material: Image

Muller supplementary material

Figure 1.tif

Download Muller supplementary material(Image)
Image 7.1 MB