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R9AP stabilizes RGS11-Gβ5 and accelerates the early light response of ON-bipolar cells

Published online by Cambridge University Press:  26 January 2010

BRETT G. JEFFREY ,
CATHERINE W. MORGANS ,
THERESA PUTHUSSERY ,
THEODORE G. WENSEL ,
NEAL S. BURKE ,
R. LANE BROWN  and
ROBERT M. DUVOISIN
BRETT G. JEFFREY*
Affiliation:
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
CATHERINE W. MORGANS
Affiliation:
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
THERESA PUTHUSSERY
Affiliation:
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
THEODORE G. WENSEL
Affiliation:
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas
NEAL S. BURKE
Affiliation:
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington
R. LANE BROWN
Affiliation:
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington
ROBERT M. DUVOISIN
Affiliation:
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon
*
*Address correspondence and reprint requests to: Brett G. Jeffrey, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006. E-mail: [email protected]
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Abstract

The rate-limiting step in the recovery of the photoreceptor light response is the hydrolysis of GTP by transducin, a reaction that is accelerated by the RGS9–Gβ5 complex, and its membrane anchor, R9AP. Similar complexes, including RGS7, RGS11, and Gβ5, are found in retinal ON-bipolar cell dendrites. Here, we present evidence that R9AP is also expressed in the dendritic tips of ON-bipolar cells. Immunofluorescent staining for R9AP revealed a punctate pattern of labeling in the outer plexiform layer, where it colocalized with mGluR6. In photoreceptors, R9AP is required for proteolytic stability of the entire regulator of G protein signaling complex, and we found that genetic deletion of R9AP also results in a marked reduction in the levels of RGS11 and Gβ5 in the bipolar cell dendrites; the level of RGS7 was unaffected, suggesting the presence of another interaction partner to stabilize RGS7. To determine the effect of R9AP deletion on the response kinetics of ON-bipolar cells, we compared the electroretinogram (ERG) between wild-type and R9AP-deficient mice. The ERG b-wave, reflecting ON-bipolar cell activity, was delayed and larger in the R9AP-deficient mice. Our data indicate that R9AP is required for stable expression of RGS11–Gβ5 in ON-bipolar cell dendrites. Furthermore, they suggest that the RGS11–Gβ5–R9AP complex accelerates the initial ON-bipolar cell response to light.

Keywords

ElectroretinogramERG b-waveRGS proteinsRetina
Type
Research Articles
Information
Visual Neuroscience , Volume 27 , Issue 1-2 , March 2010 , pp. 9 - 17
Copyright
Copyright © Cambridge University Press 2010

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References

Baker, S.A., Martemyanov, K.A., Shavkunov, A.S. & Arshavsky, V.Y. (2006). Kinetic mechanism of RGS9-1 potentiation by R9AP. Biochemistry 45, 10690–10697.Google Scholar
Berntson, A. & Taylor, W.R. (2000). Response characteristics and receptive field widths of on-bipolar cells in the mouse retina. The Journal of physiology 524(Pt 3), 879–889.CrossRefGoogle ScholarPubMed
Birch, D.G., Hood, D.C., Nusinowitz, S. & Pepperberg, D.R. (1995). Abnormal activation and inactivation mechanisms of rod transduction in patients with autosomal dominant retinitis pigmentosa and the pro-23-his mutation. Investigative Ophthalmology & Visual Science 36, 1603–1614.Google ScholarPubMed
Bloomfield, S.A. & Dowling, J.E. (1985). Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer. Journal of neurophysiology 53, 699–713.CrossRefGoogle ScholarPubMed
Cao, Y., Masuho, I., Okawa, H., Xie, K., Asami, J., Kammermeier, P.J., Maddox, D.M., Furukawa, T., Inoue, T., Sampath, A.P. & Martemyanov, K.A. (2009). Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons. The Journal of Neuroscience 29, 9301–9313.CrossRefGoogle ScholarPubMed
Cao, Y., Song, H., Okawa, H., Sampath, A.P., Sokolov, M. & Martemyanov, K.A. (2008). Targeting of RGS7/Gbeta5 to the dendritic tips of ON-bipolar cells is independent of its association with membrane anchor R7BP. The Journal of Neuroscience 28, 10443–10449.CrossRefGoogle Scholar
Chen, C.K., Burns, M.E., He, W., Wensel, T.G., Baylor, D.A. & Simon, M.I. (2000). Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature 403, 557–560.Google Scholar
Chen, C.K., Eversole-Cire, P., Zhang, H., Mancino, V., Chen, Y.J., He, W., Wensel, T.G. & Simon, M.I. (2003). Instability of GGL domain-containing RGS proteins in mice lacking the G protein beta-subunit Gbeta5. Proceedings of the National Academy of Sciences of the United States of America 100, 6604–6609.CrossRefGoogle ScholarPubMed
Chen, F.S., Shim, H., Morhardt, D., Dallman, R., Krahn, E., McWhinney, L., Rao, A., Gold, S.J. & Chen, C.-K. (2010). Functional redundancy of R7 RGS proteins in ON-bipolar cell dendrites. Investigative Ophthalmology & Visual Science 51, 686–693.Google Scholar
Cheng, J.Y., Luu, C.D., Yong, V.H., Mathur, R., Aung, T. & Vithana, E.N. (2007). Bradyopsia in an Asian man. Archives of Ophthalmology 125, 1138–1140.Google Scholar
Dhingra, A., Lyubarsky, A., Jiang, M., Pugh, E.N., Birnbaumer, L., Sterling, P. & Vardi, N. (2000). The light response of ON bipolar neurons requires G[alpha]o. The Journal of Neuroscience 20, 9053–9058.CrossRefGoogle Scholar
Dhingra, A., Sulaiman, P., Xu, Y., Fina, M.E., Veh, R.W. & Vardi, N. (2008). Probing neurochemical structure and function of retinal ON bipolar cells with a transgenic mouse. The Journal of Comparative Neurology 510, 484–496.CrossRefGoogle ScholarPubMed
Frishman, L.J. (2006). Electrogenesis of the electroretinogram. In Retina, ed., Ryan, S.J., Hinton, D.R., Schachat, A.P., Wilkinson, C.P., pp. 103–135. New York, USA: Elsevier Mosby.CrossRefGoogle Scholar
Haverkamp, S., Grünert, U. & Wässle, H. (2000). The cone pedicle, a complex synapse in the retina. Neuron 27, 85–95.Google Scholar
He, W., Cowan, C.W. & Wensel, T.G. (1998). RGS9, a GTPase accelerator for phototransduction. Neuron 20, 95–102.Google Scholar
Higashijima, T., Ferguson, K.M., Smigel, M.D. & Gilman, A.G. (1987). The effect of GTP and Mg2+ on the GTPase activity and the fluorescent properties of Go. The Journal of Biological Chemistry 262, 757–761.CrossRefGoogle ScholarPubMed
Hu, G. & Wensel, T.G. (2002). R9AP, a membrane anchor for the photoreceptor GTPase accelerating protein, RGS9-1. Proceedings of the National Academy of Sciences of the United States of America 99, 9755–9760.CrossRefGoogle ScholarPubMed
Kapousta-Bruneau, N.V. (2000). Opposite effects of GABA(A) and GABA(C) receptor antagonists on the b-wave of ERG recorded from the isolated rat retina. Vision Research 40, 1653–1665.CrossRefGoogle Scholar
Keresztes, G., Martemyanov, K.A., Krispel, C.M., Mutai, H., Yoo, P.J., Maison, S.F., Burns, M.E., Arshavsky, V.Y. & Heller, S. (2004). Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse. The Journal of Biological Chemistry 279, 1581–1584.CrossRefGoogle ScholarPubMed
Krispel, C.M., Chen, C.K., Simon, M.I. & Burns, M.E. (2003). Novel form of adaptation in mouse retinal rods speeds recovery of phototransduction. The Journal of General Physiology 122, 703–712.CrossRefGoogle ScholarPubMed
Lan, K.L., Remmers, A.E. & Neubig, R.R. (1998). Roles of G(o)alpha tryptophans in GTP hydrolysis, GDP release, and fluorescence signals. Biochemistry 37, 837–843.CrossRefGoogle ScholarPubMed
Lishko, P.V., Martemyanov, K.A., Hopp, J.A. & Arshavsky, V.Y. (2002). Specific binding of RGS9-Gbeta 5L to protein anchor in photoreceptor membranes greatly enhances its catalytic activity. The Journal of Biological Chemistry 277, 24376–24381.CrossRefGoogle ScholarPubMed
Lyubarsky, A.L., Daniele, L.L. & Pugh, E.N. (2004). From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG. Vision Research 44, 3235–3251.Google Scholar
Lyubarsky, A.L., Naarendorp, F., Zhang, X., Wensel, T., Simon, M.I. & Pugh, N.E. Jr. (2001). RGS9-1 is required for normal inactivation of mouse cone phototransduction. Molecular Vision 7, 71–78.Google ScholarPubMed
Martemyanov, K.A., Yoo, P.J., Skiba, N.P. & Arshavsky, V.Y. (2005). R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family. The Journal of Biological Chemistry 280, 5133–5136.Google Scholar
McCall, M.A., Lukasiewicz, P.D., Gregg, R.G. & Peachey, N.S. (2002). Elimination of the rho1 subunit abolishes GABA(C) receptor expression and alters visual processing in the mouse retina. The Journal of Neuroscience 22, 4163–4174.CrossRefGoogle ScholarPubMed
Mojumder, D.K., Qian, Y. & Wensel, T.G. (2009). Two R7 regulator of G-protein signaling proteins shape retinal bipolar cell signaling. The Journal of Neuroscience 29, 7753–7765.Google Scholar
Morgans, C.W., Ren, G. & Akileswaran, L. (2006). Localization of nyctalopin in the mammalian retina. The European Journal of Neuroscience 23, 1163–1171.Google Scholar
Morgans, C.W., Weiwei Liu, , Wensel, T.G., Brown, R.L., Perez-Leon, J.A., Bearnot, B. & Duvoisin, R.M. (2007). Gbeta5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells. The European Journal of Neuroscience 26, 2899–2905.Google Scholar
Morgans, C.W., Zhang, J., Jeffrey, B.G., Nelson, S., Burke, N.S., Duvoisin, R.M. & Brown, R.L. (2009). TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proceedings of the National Academy of Sciences 106, 19174–19178.CrossRefGoogle ScholarPubMed
Nakajima, Y., Iwakabe, H., Akazawa, C., Nawa, H., Shigemoto, R., Mizuno, N. & Nakanishi, S. (1993). Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. The Journal of Biological Chemistry 268, 11868–11873.Google Scholar
Nishiguchi, K.M., Sandberg, M.A., Kooijman, A.C., Martemyanov, K.A., Pott, J.W., Hagstrom, S.A., Arshavsky, V.Y., Berson, E.L. & Dryja, T.P. (2004). Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation. Nature 427, 75–78.CrossRefGoogle ScholarPubMed
Rao, A., Dallman, R., Henderson, S. & Chen, C.K. (2007). Gbeta5 is required for normal light responses and morphology of retinal ON-bipolar cells. The Journal of Neuroscience 27, 14199–14204.Google Scholar
Robson, J.G. & Frishman, L.J. (1999). Dissecting the dark-adapted electroretinogram. Documenta Ophthalmologica 95, 187–215.CrossRefGoogle Scholar
Shen, Y., Heimel, J.A., Kamermans, M., Peachey, N.S., Gregg, R.G. & Nawy, S. (2009). A transient receptor potential-like channel mediates synaptic transmission in rod bipolar cells. The Journal of Neuroscience 29, 6088–6093.CrossRefGoogle ScholarPubMed
Song, J.H., Song, H., Wensel, T.G., Sokolov, M. & Martemyanov, K.A. (2007). Localization and differential interaction of R7 RGS proteins with their membrane anchors R7BP and R9AP in neurons of vertebrate retina. Molecular and Cellular Neurosciences 35, 311–319.CrossRefGoogle ScholarPubMed
Wachtmeister, L. (1998). Oscillatory potentials in the retina: What do they reveal. Progress in Retinal and Eye Research 17, 485–521.CrossRefGoogle ScholarPubMed
Watson, A.J., Aragay, A.M., Slepak, V.Z. & Simon, M.I. (1996). A novel form of the G protein beta subunit Gbeta5 is specifically expressed in the vertebrate retina. The Journal of Biological Chemistry 271, 28154–28160.CrossRefGoogle Scholar
Werblin, F.S. & Dowling, J.E. (1969). Organization of the retina of the mudpuppy, Necturus maculosus. II. Intracellular recording. Journal of Neurophysiology 32, 339–355.CrossRefGoogle ScholarPubMed
Zhang, J., Jeffrey, B.G., Morgans, C.W., Burke, N.S., Haley, T.L., Duvoisin, R.M. & Brown, R.L. (2010). RGS7 and -11 complexes accelerate the ON-bipolar cell light response. Investigative Ophthalmology & Visual Science 51, 1121–1129.Google Scholar