Skip to main content

Phosphorylation of Non-NMDA Glutamate Receptor Ion Channels

Implications for Synaptic Plasticity and Their Membrane Topology

  • Chapter
  • 142 Accesses

Part of the book series: The Receptors ((REC))

Abstract

Modulation of physiological functions by protein phosphorylation is perhaps the most common form of cellular regulation, since up to 30% of cellular proteins can be phosphorylated (Levenson et al., 1990). Cyclic adenosine monophosphate (cAMP)-dependent protein phosphorylation was pioneered in the area of glycogen metabolism (reviewed in Krebs, 1993) in the 1950s and 1960s by Edwin Krebs and Edmond Fischer. However, it was well known from the work of Earl Sutherland (reviewed in Robison et al., 1971) that the second messenger cAMP altered many physiological processes in addition to glycogen metabolism. Thus, once the cAMP-dependent protein kinase A (PKA) was purified, it was quickly determined this kinase was multifunctional and could phosphorylate numerous proteins outside of glycogen metabolism. Other multifunctional Ser/Thr protein kinases were later characterized (e.g., casein kinases, protein kinase C [PKC], and Ca++/calmodulin-dependent protein kinase II [CaM-kinase II]), and identification of new protein kinases, including tyrosine-specific protein kinases, and their substrates proliferated during the 1970–1980s (reviewed in Hanks, 1988).

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bennett, J. A. and Dingledine, R. (1995) Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrance membrane loop. Neuron 14, 373–384.

    Article  PubMed  CAS  Google Scholar 

  • Bettler, B., Egebjerg, J., Sharma, G., Pecht, G., Hermans-Borgmeyer, I., Moll, C., Stevens, C. F., and Heinemann, S. (1992) Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit. Neuron 8, 257–265.

    Article  PubMed  CAS  Google Scholar 

  • Blackstone, C., Murphy, T. H., Moss, S. J., Baraban, J. M., and Huganir, R. L. (1994) Cyclic AMP and synaptic activity-dependent phosphorylation of AMPA-preferring glutamate receptors. J. Neurosci. 14, 7585–7593.

    PubMed  CAS  Google Scholar 

  • Bliss, T. V. P. and Collingridge, G. L. (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39.

    Article  PubMed  CAS  Google Scholar 

  • Boulter, J., Hollmann, M., O’Shea-Greenfield, A., Hrtley, M., Deneris, E., Maron, C., and Heinemann, S. (1990) Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249, 1033–1037.

    Article  PubMed  CAS  Google Scholar 

  • Browning, M. D. and Dudek, E. (1992) Activators of protein kinase C increase the phosphorylation of the synapsins at sites phosphorylated by cAMP-dependent and Ca2+/calmodulin-dependent protein kinase in the rat hippocampal slice. Synapse 10, 62–70.

    Article  PubMed  CAS  Google Scholar 

  • Carr, D. W., Stofko-Hahn, R. E., Fraser, I. D. C., Cone, R. D., and Scott, J. D. (1992) Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins: characterization of AKAP 79. J. Biol. Chem. 267, 16,816–16,823.

    CAS  Google Scholar 

  • Chen, L. and Huang, L. Y. M. (1992) Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 356, 521–523.

    Article  PubMed  CAS  Google Scholar 

  • Colombini, M., Blachly-Dyson, E., and Forte, M. (1996) VDAC, a channel in the outer mitochondrial membrane, in Ion Channels, vol. 4 (Narahashi, T., ed.), Plenum, New York, pp. 169–202.

    Google Scholar 

  • Davies, S. A., Lester, R. A. J., Reymann, K. G., and Collingridge, G. L. (1989) Temporally distinct pre- and post-synaptic mechanisms maintain long-term potentiation. Nature 338, 500–503.

    Article  PubMed  CAS  Google Scholar 

  • Fukunaga, K., Soderling, T. R., and Miyamoto, E. (1992) Activation of Ca2+/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons. J. Biol. Chem. 267, 22,527–22,533.

    CAS  Google Scholar 

  • Fukunaga, K., Stoppini, L., Miyamoto, E., and Muller, D. (1993) Long-term potentiation is associated with an increased activity of Ca2+/calmodulin-dependent protein kinase II. J. Biol. Chem. 268, 7863–7867.

    PubMed  CAS  Google Scholar 

  • Gallagher, P., Henneberry, J., Wilson, I., Sambrook, J., and Gething, M. J. (1988) Addition of carbohydrate side chains at novel sites on influenza virus hemagglutinin can modulate the folding, transport, and activity of the molecule. J. Cell Biol. 107, 2059–2073.

    Article  PubMed  CAS  Google Scholar 

  • Ginty, D. D., Kornhauser, J. M., Thompson, M. A., Bading, H., Mayo, K. E., Takahashi, J. S., and Greenberg, M. E. (1993) Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science 260, 238–241.

    Article  PubMed  CAS  Google Scholar 

  • Greengard, P., Jen, J., Nairn, A. C., and Stevens, C. F. (1991) Enhancement of the glutamate response by cAMP-dependent protein kinase in hippocampal neurons. Science 253, 1135–1138.

    Article  PubMed  CAS  Google Scholar 

  • Hanks, S. K., Quinn, A. M., and Hunter, T. (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241, 42–52.

    Article  PubMed  CAS  Google Scholar 

  • Hanson, P. I., and Schulman, H. (1992) Neuronal Ca2+/calmodulin-dependent protein kinases. Annu. Rev. Biochem. 61, 559–601.

    Article  PubMed  CAS  Google Scholar 

  • Hollmann, M., Maron, C., and Heinemann, S. (1994) N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron 13, 1331–1343.

    Article  PubMed  CAS  Google Scholar 

  • Ito, I., Hidaka, H., and Sugiyama, H. (1991) Effects of KN-62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, on a long-term potentiation in the rat hippocampus. Neurosci. Lett. 121, 1119–1121.

    Article  Google Scholar 

  • Keinanen, K., Wisden, W., Sommer, B., Werner, P., Herb, A., Verdoorn, T. A., Sakmann, B., and Seeburg, P. H. (1990) A family of AMPA-selective glutamate receptors. Science 249, 556–560.

    Article  PubMed  CAS  Google Scholar 

  • Keller, B. U., Hollmann, M., Heinemann, S., and Konnerth, A. (1992) Calcium influx through subunits GluR1GluR3 of kainate/AMPA receptor channels is regulated by cAMP dependent protein kinase. EMBO J. 11, 891–896.

    PubMed  CAS  Google Scholar 

  • Kelly, P. T., McGuiness, T. L., and Greengard, P. (1984) Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase. Proc. Natl Acad. Sci. USA 81, 945–949.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, M. B., Bennett, M. K., and Erondu, N. G. (1983) Biochemical and immunochemical evidence that the “major postsynaptic density protein” is a subunit of calmodulin-dependent protein kinase. Proc. Natl. Acad. Sci. USA 80, 7357–7361.

    Article  PubMed  CAS  Google Scholar 

  • Knapp, A. G. and Dowling, J. E. (1987) Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells. Nature 325, 437–439.

    Article  PubMed  CAS  Google Scholar 

  • Kolaj, M., Cerne, R., Cheng, G., Brickey, D. A., and Randic, M. (1994) Alpha sub-unit of calcium/calmodulin-dependent protein kinase enhances excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons. J. Neurophysiol. 72, 2525–2531.

    PubMed  CAS  Google Scholar 

  • Krebs, E. G. (1993) Nobel lecture. Protein phosphorylation and cellular regulation I. Biosci. Rep. 13, 127–142.

    Article  PubMed  CAS  Google Scholar 

  • Kullmann, D. M., Perkel, D. J., Manabe, T., and Nicoll, R. A. (1992) Ca2+ entry via postsynaptic voltage-sensitive Ca2+ channels can transiently potentiate excitatory synaptic transmission in the hippocampus. Neuron 9, 1175–1183.

    Article  PubMed  CAS  Google Scholar 

  • Levenson, R. M., Anderson, G. M., Cohn, J. A., and Blackshear, P. J. (1990) Giant two-dimensional gel electrophoresis: methodological update and comparison with intermediate-format gel systems. Electrophoresis 11, 269–279.

    Article  PubMed  CAS  Google Scholar 

  • Liman, E. R., Knapp, A. G., and Dowling, J. E. (1989) Enhancement of kainate-gated currents in retinal horizontal cells by cAMP-dependent protein kinase. Brain Res. 481, 399–402.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y. C., and Storm, D. R. (1990) Regulation of free calmodulin levels by neuromodulin: neuron growth and regeneration. Trends Pharmacol. Sci. 11, 107–111.

    Article  PubMed  CAS  Google Scholar 

  • Lledo, P. M., Hjelmstad, G., Mukherji, S., Soderling, T. R., Malenka, R. C., and Nicoll, R. A. (1995) CaM-kinase II and LTP enhance synaptic transmission by the same mechanism. Proc. Natl. Acad. Sci. USA 92, 11,175–11,179.

    Article  CAS  Google Scholar 

  • Lynch, G., Larson, J., Kelso, S., Barrionuevo, G., and Schottler, F. (1983) Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305, 719–721.

    Article  PubMed  CAS  Google Scholar 

  • MacDonald, R. L. and Olsen, R. W. (1994) GABAA receptor channels. Annu. Rev. Neurosci. 17, 569–602.

    Article  PubMed  CAS  Google Scholar 

  • MacNicol, N. and Schulman, H. (1992) Cross-talk between protein kinase C and multifunctional Ca2+/calmodulin-dependent protein kinase. J. Biol Chem. 267, 12,197–12,201.

    CAS  Google Scholar 

  • Malenka, R. C. (1991) The role of postsynaptic calcium in the induction of long-term potentiation. Mol. Neurobiol. 5, 289–295.

    Article  PubMed  CAS  Google Scholar 

  • Malinow, R., Schulman, H., and Tsien, R. W. (1989) Inhibition of postsynaptic pKC or CaM-KII blocks induction but not expression of LTP. Science 245, 862–866.

    Article  PubMed  CAS  Google Scholar 

  • McGlade-McCulloh, E., Yamamoto, H., Tan, S. E., Brickey, D. A., and Soderling, T. R. (1993) Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II. Nature 362, 640–642.

    Article  PubMed  CAS  Google Scholar 

  • Moln’ar, E., Baude, A., Patel, P. B., Somogyi, P., and McLlhinney, R. A. (1993) Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit. Neurosci. 53, 307–326.

    Article  Google Scholar 

  • Nakazawa, K., Mikawa, S., Hashikawa, T., and Ito, M. (1995) Transient and persistent phosphorylations of AMPA-type glutamate receptor subunits in cerebellar purkinje cells. Neuron 15, 697–709.

    Article  PubMed  CAS  Google Scholar 

  • Ortega, A., and Teichberg, V. I. (1990) Phosphorylation of the 49-kDA putative subunit of the chick cerebellar kainate receptor and its regulation by kainatergic ligands. J. Biol. Chem. 265, 21,404–21,406.

    CAS  Google Scholar 

  • Petralia, R. S. and Wenthold, R. J. (1992) Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in the rat brain. J. Comp. Neurol. 318, 329–354.

    Article  PubMed  CAS  Google Scholar 

  • Pettit, D. L., Perlman, S., and Malinow, R. (1994) Potentiated transmission and prevention of further LTP by increased CaM-KII activity in postsynaptic hippocampal slice neurons. Science 266, 1881–1885.

    Article  PubMed  CAS  Google Scholar 

  • Raymond, L. A., Blackstone, C. D., and Huganir, R. L. (1993) Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase. Nature 361, 637–641.

    Article  PubMed  CAS  Google Scholar 

  • Reymann, K. G. (1993) Mechanisms underlying synaptic long-term potentiation in the hippocampus: focus on postsynaptic glutamate receptors and protein kinases. Functional Neurol. (Suppl. 8), 7–32.

    Google Scholar 

  • Robison, G. A., Butcher, R. W., and Sutherland, E. W. (1971) Cyclic AMP. Academic, New York.

    Google Scholar 

  • Roche, K. W., O’Brien, R. J., Mammen, A. L., Bernhardt, J., and Huganir, R. L. (1996) Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16, 1179–1188.

    Article  PubMed  CAS  Google Scholar 

  • Roche, K. W., Raymond, L. A., Blackstone, C., and Huganir, R. L. (1994a) Transmembrane topology of the glutamate receptor subunit GluR6. J. Biol. Chem. 269, 11,679–11,682.

    CAS  Google Scholar 

  • Roche, K. W., Tingley, W., and Huganir, R. L. (1994b) Glutamate receptor phosphorylation and synaptic plasticity. Curr. Opin. Neurobiol. 4, 383–388.

    Article  PubMed  CAS  Google Scholar 

  • Rosenmund, C., Carr, D. W., Dergeson, S. E., Nilaver, G., Scott, J. D., and Westbrook, G. L. (1994) Anchoring of protein kinase A is required for modulation of AMPA/ kainate receptors on hippocampal neurons. Nature 368, 853–856.

    Article  PubMed  CAS  Google Scholar 

  • Silva, A. J., Paylor, R., Wehner, J. M., and Tonegawa, S. (1992a) Impaired spatial learning in a-calcium-calmodulin kinase II mutant mice. Science 257, 206–209.

    Article  PubMed  CAS  Google Scholar 

  • Silva, A. J., Stevens, C. F., Tonegawa, S., and Wang, Y. (1992b) Deficient hippocampal long-term potentiation in α-calcium-calmodulin kinase II mutant mice. Science 257, 201–206.

    Article  PubMed  CAS  Google Scholar 

  • Slatin, S. L., Qiu, X. Q., Jakes, K. S., and Finkelstein, A. (1994) Identification of a translocated protein segment in a voltage-dependent channel. Nature 371, 158–161.

    Article  PubMed  CAS  Google Scholar 

  • Soderling, T. R. (1995) Calcium-dependent protein kinases in learning and memory, in Advances in Second Messenger and Phosphoprotein Research, vol. 30 (Means, A. R., ed.), Raven, New York, pp. 175–189.

    Google Scholar 

  • Stern-Bach, Y., Bettler, B., Hartley, M., Sheppard, P. O., O’Hare, P. J., and Heinemann, S. F. (1994) Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13, 1345–1357.

    Article  PubMed  CAS  Google Scholar 

  • Susuki, T., Okumura-Noji, K., Ogura, A., Kudo, Y., and Tanaka, R. (1992) Antibody specific for the Thr-286-autophosphorylated alpha subunit of Ca2+/calmodulin-dependent protein kinase II. Proc. Natl. Acad. Sci. USA 89, 109–113.

    Article  Google Scholar 

  • Swope, S. L., Moss, S. J., Blackstone, C. D., and Huganir, R. L. (1992) Phosphorylation of ligand-gated ion channels: a possible mode of synaptic plasticity. FASEB J. 6, 2514–2523.

    PubMed  CAS  Google Scholar 

  • Tan, S. E., Wenthold, R. J., and Soderling, T. R. (1994) Phosphorylation of AMPA-type glutamate receptors by calcium/calmodulin-dependent protein kinase II and protein kinase C in cultured hippocampal neurons. J. Neurosci. 14, 1123–1129.

    PubMed  CAS  Google Scholar 

  • Taverna, F., Wang, L. Y., MacDonald, J. F., and Hampson, D. R. (1994) A transmembrane model for an ionotropic glutamate receptor predicted on the basis of the location of asparagine-linked oligosaccharides. J. Biol Chem. 269, 14,159–14,164.

    CAS  Google Scholar 

  • Tingley, W. G., Roche, K. W., Thompson, A. K., and Huganir, R. L. (1993) Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain. Nature 364, 70–73.

    Article  PubMed  CAS  Google Scholar 

  • Urushihara, H., Tohda, M., and Nomura, Y. (1992) Selective potentiation of N-methyl-D-aspartate-induced current by protein kinase C in Xenopus oocytes injected with rat brain RNA. J. Biol Chem. 267, 11,697–11,700.

    CAS  Google Scholar 

  • Wang, L. Y., Dudek, E. M., Browning, M. D., and MacDonald, J. F. (1994) Modulation of AMPA/kainate receptors in cultured murine hippocampal neurones by protein kinase C. J. Physiol 475(3), 431–437.

    PubMed  CAS  Google Scholar 

  • Wang, L. Y., Salter, M. W., and MacDonald, J. F. (1991) Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases. Science 253, 1132–1135.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L. Y., Taverna, F. A., Huang, X. P., MacDonald, J. F., and Hampson, D. R. (1993) Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase. Science 259, 1173–1175.

    Article  PubMed  CAS  Google Scholar 

  • Wyllie, D. J. A. and Nicoll, R. A. (1994) A role for protein kinases and phosphatases in the Ca2+-induced enhancement of hippocampal AMPA receptor-mediated synaptic responses. Neuron 13, 635–643.

    Article  PubMed  CAS  Google Scholar 

  • Yakel, J. L., Vissavajhala, P., Derkach, V. A., Brickey, D. A., and Soderling, T. R. (1995) Identification of a Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in non-N-methyl-D-aspartate glutamate receptors. Proc. Natl Acad. Sci. USA 92, 1376–1380.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Humana Press Inc.

About this chapter

Cite this chapter

Soderling, T.R. (1997). Phosphorylation of Non-NMDA Glutamate Receptor Ion Channels. In: Monaghan, D.T., Wenthold, R.J. (eds) The Ionotropic Glutamate Receptors. The Receptors. Humana Press. https://doi.org/10.1007/978-1-4612-3962-8_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-3962-8_5

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-8442-0

  • Online ISBN: 978-1-4612-3962-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics