Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-24T01:44:57.920Z Has data issue: false hasContentIssue false
  • English
  • Français

G protein coupling profile of mGluR6 and expression of Gα proteins in retinal ON bipolar cells

Published online by Cambridge University Press:  30 January 2007

LIANTIAN TIAN  and
PAUL J. KAMMERMEIER
LIANTIAN TIAN
Affiliation:
Department of Biomedical Sciences, Kent State University, and the Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
PAUL J. KAMMERMEIER
Affiliation:
Department of Pharmacology and Physiology, the University of Rochester, Rochester, New York
Get access Rights & Permissions [Opens in a new window]

Abstract

Metabotropic glutamate receptor 6 (mGluR6) is a group III, pertussis toxin (PTX)-sensitive G protein coupled mGluR that plays a specialized role in the retina. Retinal ON bipolar cells, which receive direct glutamatergic input from photoreceptor cells, express mGluR6 as their primary postsynaptic glutamate receptor. Activation of mGluR6 in these cells initiates an intracellular signaling cascade ultimately leading to inhibition of a cation channel and cell hyperpolarization. The primary mediator of this pathway in vivo is Gαo, but the potential roles of other G proteins from the Gαi/o family in the regulation of this or other signaling pathways in ON bipolar cells are unclear. To determine which specific G proteins from the Gαi/o family are able to couple to mGluR6, a Gα reconstitution system was employed using PTX-insensitive Gα mutants expressed with mGluR6 in PTX-treated sympathetic neurons from the rat superior cervical ganglion (SCG). The efficiency of coupling to mGluR6 was Goa > Gob, Gi1 > Gi2, Gi3, whereas no coupling was observed with Gαz, nor with the retinal Gα proteins, rod (GNAT2) or cone (GNAT1) transducin (GαTr-R, GαTr-C). Finally, the expression of Gα proteins determined to couple with mGluR6 was examined in rat ON bipolar cells using single cell RT-PCR. Co-expression of mGluR6 message was used to distinguish ON from OFF bipolar cells. Expression of Gαo was detected in every ON bipolar cell examined. Message for Gαi1, which coupled moderately to mGluR6, was not detected in ON bipolar cells, nor was Gαi3, which coupled to mGluR6 in only a few cells but on average did not exhibit statistically significant coupling. Finally, though Gαi2 was detectable in ON bipolar cells, its coupling to mGluR6 in the SCG system was not significant. Together, these data indicate that signaling through mGluR6 in mammalian ON bipolar cells is highly focused, apparently acting through a single Gα protein subtype.

Keywords

mGluRRetinaPertussis toxinG protein Coupled receptor
Type
Research Article
Information
Visual Neuroscience , Volume 23 , Issue 6 , November 2006 , pp. 909 - 916
Copyright
© 2006 Cambridge University Press

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

REFERENCES

Bahia, D.S., Wise, A., Fanelli, F., Lee, M., Rees, S., & Milligan, G. (1998). Hydrophobicity of residue351 of the G protein Gi1 alpha determines the extent of activation by the alpha 2A-adrenoceptor. Biochemistry 37, 11555–11562.CrossRefGoogle Scholar
Bean, B.P. (1989). Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. Nature 340, 153–156.CrossRefGoogle Scholar
Bradley, S.R., Levey, A.I., Hersch, S.M., & Conn, P.J. (1996). Immunocytochemical localization of group III metabotropic glutamate receptors in the hippocampus with subtype-specific antibodies. The Journal of Neuroscience 16, 2044–2056.Google Scholar
Dhingra, A., Faurobert, E., Dascal, N., Sterling, P., & Vardi, N. (2004). A retinal-specific regulator of G-protein signaling interacts with Galpha(o) and accelerates an expressed metabotropic glutamate receptor 6 cascade. The Journal of Neuroscience 24, 5684–5693.Google Scholar
Dhingra, A., Jiang, M., Wang, T.L., Lyubarsky, A., Savchenko, A., Bar-Yehuda, T., Sterling, P., Birnbaumer, L., & Vardi, N. (2002). Light response of retinal ON bipolar cells requires a specific splice variant of Galpha(o). The Journal of Neuroscience 22, 4878–4884.Google Scholar
Dhingra, A., Lyubarsky, A., Jiang, M., Pugh, E.N., Jr., Birnbaumer, L., Sterling, P., & Vardi, N. (2000). The light response of ON bipolar neurons requires Gαo. The Journal of Neuroscience 20, 9053–9058.Google Scholar
Doupnik, C.A., Xu, T., & Shinaman, J.M. (2001). Profile of RGS expression in single rat atrial myocytes. Biochim et Biophysica Acta 1522, 97–107.CrossRefGoogle Scholar
Elmslie, K.S., Zhou, W., & Jones, S.W. (1990). LHRH and GTP-γ-S modify calcium current activation in bullfrog sympathetic neurons. Neuron 5, 75–80.CrossRefGoogle Scholar
Garcia, D.E., Li, B., Garcia-Ferreiro, R.E., Hernandez-Ochoa, E.O., Yan, K., Gautam, N., Catterall, W.A., Mackie, K., & Hille, B. (1998). G-protein β-subunit specificity in the fast membrane-delimited inhibition of Ca2+ channels. The Journal of Neuroscience 18, 9163–9170.Google Scholar
Herlitze, S., Garcia, D.E., Mackie, K., Hille, B., Scheuer, T., & Catterall, W. (1996). Modulation of Ca2+ channels by G-protein βγ subunits. Nature 380, 258–262.CrossRefGoogle Scholar
Hille, B. (1994). Modulation of ion channel function by G-protein coupled receptors. Trends in Neurosciences 17, 531–535.CrossRefGoogle Scholar
Ikeda, S.R. (1996). Voltage-dependent modulation of N-type calcium channels by G-protein βγ subunits. Nature 380, 255–258.CrossRefGoogle Scholar
Ikeda, S.R. (1997). Heterologous expression of receptors and signaling proteins in adult mammalian sympathetic neurons by microinjection. In Methods in Molecular Biology, vol. 83. ed. Challis, R.A.J., pp. 191–202. Totowa, NJ: Humana Press, Inc.
Ikeda, S.R., Lovinger, D.M., Mccool, B.A., & Lewis, D.L. (1995). Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: Subtype-specific coupling to ion channels. Neuron 14, 1029–1038.CrossRefGoogle Scholar
Jeong, S.-W. & Ikeda, S.R. (1998). G protein α subunit Gaz couples neurotransmitter receptors to ion channels in sympathetic neurons. Neuron 21, 1201–1212.CrossRefGoogle Scholar
Jeong, S.W. & Ikeda, S.R. (2000). Endogenous regulator of G-protein signaling proteins modify N-type calcium channel modulation in rat sympathetic neurons. The Journal of Neuroscience 20, 4489–4496.Google Scholar
Kammermeier, P.J., Davis, M.I., & Ikeda, S.R. (2003). Specificity of metabotropic glutamate receptor 2 coupling to G proteins. Molecular Pharmacology 63, 183–191.CrossRefGoogle Scholar
Krapivinsky, G., Krapivinsky, L., Wickman, K., & Clapham, D.E. (1995). G beta gamma binds directly to the G protein-gated K+ channel, IKACh. The Journal of Biological Chemistry 270, 29059–29062.CrossRefGoogle Scholar
Lujan, R., Nusser, Z., Roberts, J.D., Shigemoto, R., & Somogyi, P. (1996). Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus. The European Journal of Neurosciences 8, 1488–1500.CrossRefGoogle Scholar
Macek, T.A., Schaffhauser, H., & Conn, P.J. (1999). Activation of PKC disrupts presynaptic inhibition by group II and group III metabotropic glutamate receptors and uncouples the receptor from GTP-binding proteins. Annals of the New York Academy of Science 868, 554–557.CrossRefGoogle Scholar
Masland, R.H. (2001). The fundamental plan of the retina. Nature Neuroscience 4, 877–886.CrossRefGoogle Scholar
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
Nawy, S. (1999). The metabotropic receptor mGluR6 may signal through G(o), but not phosphodiesterase, in retinal bipolar cells. The Journal of Neuroscience 19, 2938–2944.Google Scholar
Nomura, A., Shigemoto, R., Nakamura, Y., Okamoto, N., Mizuno, N., & Nakanishi, S. (1994). Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Cell 77, 361–369.CrossRefGoogle Scholar
Pan, Z.H. & Hu, H.J. (2000). Voltage-dependent Na(+) currents in mammalian retinal cone bipolar cells. Journal of Neurophysiology 84, 2564–2571.Google Scholar
Pan, Z.H. & Lipton, S.A. (1995). Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals. The Journal of Neuroscience 15, 2668–2679.Google Scholar
Penela, P., Ribas, C., & Mayor, F., Jr. (2003). Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases. Cell Signal 15, 973–981.CrossRefGoogle Scholar
Pin, J.-P. & Duvoisin, R. (1995). Neurotransmitter receptors I. The metabotropic glutamate receptors: Structure and functions. Neuropharmacology 34, 1–26.Google Scholar
Pisani, A., Calabresi, P., Centonze, D., & Bernardi, G. (1997). Activation of group III metabotropic glutamate receptors depresses glutamatergic transmission at corticostriatal synapse. Neuropharmacology 36, 845–851.CrossRefGoogle Scholar
Rosemond, E., Peltekova, V., Naples, M., Thogersen, H., & Hampson, D.R. (2002). Molecular determinants of high affinity binding to group III metabotropic glutamate receptors. The Journal of Biological Chemistry 277, 7333–7340.CrossRefGoogle Scholar
Ruiz-Velasco, V. & Ikeda, S.R. (2000). Multiple G-protein betagamma combinations produce voltage-dependent inhibition of N-type calcium channels in rat superior cervical ganglion neurons. The Journal of Neuroscience 20, 2183–2191.Google Scholar
Schoepp, D.D. & Conn, P.J. (1993). Metabotropic glutamate receptors in brain function and pathology. Trends in Pharmacological Sciences 14, 13–20.CrossRefGoogle Scholar
Seifert, G., Rehn, L., Weber, M., & Steinhauser, C. (1997). AMPA receptor subunits expressed by single astrocytes in the juvenile mouse hippocampus. Brain Research Molecular Brain Research 47, 286–294.CrossRefGoogle Scholar
Stehno-Bittel, L., Krapivinsky, G., Krapivinsky, L., Perez-Terzic, C., & Clapham, D.E. (1995). The G protein beta gamma subunit transduces the muscarinic receptor signal for Ca2+ release in Xenopus oocytes. The Journal of Biological Chemistry 270, 30068–30074.Google Scholar
Tachibana, M. & Kaneko, A. (1987). gamma-Aminobutyric acid exerts a local inhibitory action on the axon terminal of bipolar cells: Evidence for negative feedback from amacrine cells. Proceedings of the National Academy of Sciences of the United States of America 84, 3501–3505.CrossRefGoogle Scholar
Weng, K., Lu, C., Daggett, L.P., Kuhn, R., Flor, P.J., Johnson, E.C., & Robinson, P.R. (1997). Functional coupling of a human retinal metabotropic glutamate receptor (hmGluR6) to bovine rod transducin and rat Go in an in vitro reconstitution system. The Journal of Biological Chemistry 272, 33100–33104.CrossRefGoogle Scholar
Wu, S., Wright, R.A., Rockey, P.K., Burgett, S.G., Arnold, J.S., Rosteck, P.R., Jr., Johnson, B.G., Schoepp, D.D., & Belagaje, R.M. (1998). Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. Brain Research. Molecular Brain Research 53, 88–97.CrossRefGoogle Scholar
Yeh, H.H., Lee, M.B., & Cheun, J.E. (1990). Properties of GABA-activated whole-cell currents in bipolar cells of the rat retina. Visual Neuroscience 4, 349–357.CrossRefGoogle Scholar