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Increased A-to-I RNA editing of the transcript for GABAA receptor subunit α3 during chick retinal development

Published online by Cambridge University Press:  16 September 2010

HENRIK RING ,
HENRIK BOIJE ,
CHAMMIRAN DANIEL ,
JOHAN OHLSON ,
MARIE ÖHMAN  and
FINN HALLBÖÖK
HENRIK RING
Affiliation:
Department of Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden
HENRIK BOIJE
Affiliation:
Department of Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden
CHAMMIRAN DANIEL
Affiliation:
Department of Molecular Biology & Functional Genomics, Stockholm University, Stockholm, Sweden
JOHAN OHLSON
Affiliation:
Department of Molecular Biology & Functional Genomics, Stockholm University, Stockholm, Sweden
MARIE ÖHMAN
Affiliation:
Department of Molecular Biology & Functional Genomics, Stockholm University, Stockholm, Sweden
FINN HALLBÖÖK*
Affiliation:
Department of Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden
*
†Address correspondence and reprint requests to: Finn Hallböök, Department of Neuroscience, Biomedical Center (BMC), Uppsala University, Box 593, 751 24 Uppsala, Sweden. E-mail: Finn.hallbook@neuro.uu.se
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Abstract

Adenosine-to-inosine (A-to-I) RNA editing is a cotranscriptional or posttranscriptional gene regulatory mechanism that increases the diversity of the proteome in the nervous system. Recently, the transcript for GABA type A receptor subunit α3 was found to be subjected to RNA editing. The aim of this study was to determine if editing of the chicken α3 subunit transcript occurs in the retina and if the editing is temporally regulated during development. We also raised the question if editing of the α3 transcript was temporally associated with the suggested developmental shift from excitation to inhibition in the GABA system. The editing frequency was studied by using Sanger and Pyrosequencing, and to monitor the temporal aspects, we studied the messenger RNA expression of the GABAA receptor subunits and chloride pumps, known to be involved in the switch. The results showed that the chick α3 subunit was subjected to RNA editing, and its expression was restricted to cells in the inner nuclear and ganglion cell layer in the retina. The extent of editing increased during development (after embryonic days 8–9) concomitantly with an increase of expression of the chloride pump KCC2. Expression of several GABAA receptor subunits known to mediate synaptic GABA actions was upregulated at this time. We conclude that editing of the chick GABAA subunit α3 transcript in chick retina gives rise to an amino acid change that may be of importance in the switch from excitatory to inhibitory receptors.

Keywords

Chloride ion channelGABA(A) subunitsGABA receptorKCC2mRNA expressionPosttranscriptional modification

Information

Type
Research Articles
Information
Visual Neuroscience , Volume 27 , Issue 5-6 , November 2010 , pp. 149 - 157
Copyright
Copyright © Cambridge University Press 2010

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References

Andäng, M., Hjerling-Leffler, J., Moliner, A., Lundgren, T.K., Castelo-Branco, G., Nanou, E., Pozas, E., Bryja, V., Halliez, S., Nishimaru, H., Wilbertz, J., Arenas, E., Koltzenburg, M., Charnay, P., El Manira, A., Ibanez, C.F. & Ernfors, P. (2008). Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature 451, 460–464.CrossRefGoogle ScholarPubMed
Behar, T.N., Li, Y.X., Tran, H.T., Ma, W., Dunlap, V., Scott, C. & Barker, J.L. (1996). GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms. The Journal of Neuroscience 16, 1808–1818.CrossRefGoogle ScholarPubMed
Belelli, D., Harrison, N.L., Maguire, J., Macdonald, R.L., Walker, M.C. & Cope, D.W. (2009). Extrasynaptic GABAA receptors: Form, pharmacology, and function. The Journal of Neuroscience 29, 12757–12763.CrossRefGoogle ScholarPubMed
Ben-Ari, Y. (2002). Excitatory actions of gaba during development: the nature of the nurture. Nature Review. Neuroscience 3, 728–739.CrossRefGoogle ScholarPubMed
Ben-Ari, Y., Gaiarsa, J.L., Tyzio, R. & Khazipov, R. (2007). GABA: A pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiological Review 87, 1215–1284.CrossRefGoogle Scholar
Boije, H., Edqvist, P.H. & Hallböök, F. (2008). Temporal and spatial expression of transcription factors FoxN4, Ptf1a, Prox1, Isl1 and Lim1 mRNA in the developing chick retina. Gene Expression Patterns 8, 117–123.CrossRefGoogle ScholarPubMed
Brusa, R., Zimmermann, F., Koh, D.S., Feldmeyer, D., Gass, P., Seeburg, P.H. & Sprengel, R. (1995). Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science 270, 1677–1680.CrossRefGoogle ScholarPubMed
da Silva, R.T., Hokoc, J.N., de Mello, F.G. & Gardino, P.F. (2009). Differential immunodetection of L-DOPA decarboxylase and tyrosine hydroxylase in the vertebrate retina. International Journal of Developmental Neuroscience 27, 469–476.CrossRefGoogle ScholarPubMed
Daniel, C. & Öhman, M. (2009). RNA editing and its impact on GABAA receptor function. Biochemical Society Transactions 37, 1399–1403.CrossRefGoogle ScholarPubMed
Farrant, M. & Kaila, K. (2007). The cellular, molecular and ionic basis of GABA(A) receptor signalling. Progress in Brain Research 160, 59–87.CrossRefGoogle ScholarPubMed
Feldmeyer, D., Kask, K., Brusa, R., Kornau, H.C., Kolhekar, R., Rozov, A., Burnashev, N., Jensen, V., Hvalby, O., Sprengel, R. & Seeburg, P.H. (1999). Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Nature Neuroscience 2, 57–64.CrossRefGoogle Scholar
Fisher, J.L. (2004). A mutation in the GABAA receptor alpha 1 subunit linked to human epilepsy affects channel gating properties. Neuropharmacology 46, 629–637.CrossRefGoogle ScholarPubMed
Gardino, P.F., dos Santos, R.M. & Hokoc, J.N. (1993). Histogenesis and topographical distribution of tyrosine hydroxylase immunoreactive amacrine cells in the developing chick retina. Brain Research Developmental Brain Research 72, 226–236.CrossRefGoogle ScholarPubMed
Greferath, U., Grunert, U., Fritschy, J.M., Stephenson, A., Mohler, H. & Wassle, H. (1995). GABAA receptor subunits have differential distributions in the rat retina: In situ hybridization and immunohistochemistry. The Journal of Comparative Neurology 353, 553–571.CrossRefGoogle ScholarPubMed
Gustincich, S., Feigenspan, A., Sieghart, W. & Raviola, E. (1999). Composition of the GABA(A) receptors of retinal dopaminergic neurons. The Journal of Neuroscience 19, 7812–7822.CrossRefGoogle ScholarPubMed
Hamburger, V. & Hamilton, H.L. (1951). A series of normal stages in the development of the chick embryo. Journal of Morphology 88, 49–92.CrossRefGoogle ScholarPubMed
Hevers, W. & Lüddens, H. (1998). The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. Molecular Neurobiology 18, 35–86.CrossRefGoogle ScholarPubMed
Jepson, J.E. & Reenan, R.A. (2008). RNA editing in regulating gene expression in the brain. Biochimica et Biophysica Acta 1779, 459–470.CrossRefGoogle ScholarPubMed
Koulen, P. (1999). Postnatal development of GABAA receptor beta1, beta2/3, and gamma2 immunoreactivity in the rat retina. The Journal of Neuroscience Research 57, 185–194.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Koulen, P., Sassoe-Pognetto, M., Grunert, U. & Wassle, H. (1996). Selective clustering of GABA(A) and glycine receptors in the mammalian retina. The Journal of Neuroscience 16, 2127–2140.CrossRefGoogle ScholarPubMed
Laurie, D.J., Seeburg, P.H. & Wisden, W. (1992 a). The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. The Journal of Neuroscience 12, 1063–1076.CrossRefGoogle ScholarPubMed
Laurie, D.J., Wisden, W. & Seeburg, P.H. (1992 b). The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. The Journal of Neuroscience 12, 4151–4172.CrossRefGoogle ScholarPubMed
LoTurco, J.J., Owens, D.F., Heath, M.J., Davis, M.B. & Kriegstein, A.R. (1995). GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15, 1287–1298.CrossRefGoogle ScholarPubMed
Lüddens, H., Pritchett, D.B., Kohler, M., Killisch, I., Keinanen, K., Monyer, H., Sprengel, R. & Seeburg, P.H. (1990). Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature 346, 648–651.CrossRefGoogle ScholarPubMed
Maydanovych, O. & Beal, P.A. (2006). Breaking the central dogma by RNA editing. Chemical Review 106, 3397–3411.CrossRefGoogle ScholarPubMed
Nguyen, L., Malgrange, B., Breuskin, I., Bettendorff, L., Moonen, G., Belachew, S. & Rigo, J.M. (2003). Autocrine/paracrine activation of the GABA(A) receptor inhibits the proliferation of neurogenic polysialylated neural cell adhesion molecule-positive (PSA-NCAM+) precursor cells from postnatal striatum. The Journal of Neuroscience 23, 3278–3294.CrossRefGoogle Scholar
Nimmich, M.L., Heidelberg, L.S. & Fisher, J.L. (2009). RNA editing of the GABA(A) receptor alpha3 subunit alters the functional properties of recombinant receptors. Neuroscience Research 63, 288–293.CrossRefGoogle ScholarPubMed
Ohlson, J., Pedersen, J.S., Haussler, D. & Öhman, M. (2007). Editing modifies the GABA(A) receptor subunit alpha3. RNA 13, 698–703.CrossRefGoogle ScholarPubMed
Pringle, N. (2006). Non-radioactive in situ hybridization with digoxygenin (DIG)-labelled probes.Protocol is available from: http://www.ucl.ac.uk/∼ucbzwdr/methods.htm#Non-radioactiveGoogle Scholar
Represa, A. & Ben-Ari, Y. (2005). Trophic actions of GABA on neuronal development. Trends in Neuroscience 28, 278–283.CrossRefGoogle ScholarPubMed
Rivera, C., Voipio, J., Payne, J.A., Ruusuvuori, E., Lahtinen, H., Lamsa, K., Pirvola, U., Saarma, M. & Kaila, K. (1999). The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397, 251–255.CrossRefGoogle Scholar
Rula, E.Y., Lagrange, A.H., Jacobs, M.M., Hu, N., Macdonald, R.L. & Emeson, R.B. (2008). Developmental modulation of GABA(A) receptor function by RNA editing. The Journal of Neuroscience 28, 6196–6201.CrossRefGoogle ScholarPubMed
Seeburg, P.H. (2002). A-to-I editing: New and old sites, functions and speculations. Neuron 35, 17–20.CrossRefGoogle ScholarPubMed
Spira, A.W., Millar, T.J., Ishimoto, I., Epstein, M.L., Johnson, C.D., Dahl, J.L. & Morgan, I.G. (1987). Localization of choline acetyltransferase-like immunoreactivity in the embryonic chick retina. The Journal of Comparative Neurology 260, 526–538.CrossRefGoogle ScholarPubMed
Wahlstedt, H., Daniel, C., Enstero, M. & Öhman, M. (2009). Large-scale mRNA sequencing determines global regulation of RNA editing during brain development. Genome Research 19, 978–986.CrossRefGoogle ScholarPubMed
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A. & Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3, RESEARCH0034.CrossRefGoogle ScholarPubMed
Wang, D.D. & Kriegstein, A.R. (2009). Defining the role of GABA in cortical development. The Journal Physiology 587, 1873–1879.CrossRefGoogle ScholarPubMed
Wisden, W., Laurie, D.J., Monyer, H. & Seeburg, P.H. (1992). The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. The Journal of Neuroscience 12, 1040–1062.CrossRefGoogle Scholar
Zhang, L.L., Delpire, E. & Vardi, N. (2007). NKCC1 does not accumulate chloride in developing retinal neurons. Journal of Neurophysiology 98, 266–277.CrossRefGoogle Scholar
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