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Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation

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Abstract

Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently utilized for the analysis of the molecular mechanisms of memory formation. Extensive studies have demonstrated that various kinases and phosphatases regulate neuronal plasticity by phosphorylating and dephosphorylating proteins essential to the basic processes of adaptive changes in the CNS. These proteins include receptors, ion channels, synaptic vesicle proteins, and nuclear proteins. Multifunctional kinases (cAMP-dependent protein kinase, Ca2+/phospholipid-dependent protein kinase, and Ca2+/calmodulin-dependent protein kinases) and phosphatases (calcineurin, protein phosphatases 1, and 2A) that specifically modulate the phosphorylation status of neuronal-signaling proteins have been shown to be required for neuronal plasticity. In general, kinases are involved in upregulation of the activity of target substrates, and phosphatases downregulate them. Although this rule is applicable in most of the cases studied, there are also a number of exceptions. A variety of regulation mechanisms via phosphorylation and dephosphorylation mediated by multiple kinases and phosphatases are discussed.

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References

  • Agopyan N., Tokutomi N., and Akaike N. (1993) Protein kinase A-mediated phosphorylation reduces only the fast desensitizing glycine current in acutely dissociated ventromedial hypothalamic neurons.Neuroscience 56, 605–615.

    Article  PubMed  CAS  Google Scholar 

  • Aigner L., Arber S., Kapfhammer J. P., Laux T., Schneider C., Botteri F., Brenner H. R., and Caroni P. (1995) Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice.Cell 83, 269–278.

    Article  PubMed  CAS  Google Scholar 

  • Ambrose C., James M., Barnes G., Lin C., Bates G., Altherr M., Duyao M., Groot N., Church D., and Wasmuth J. J. (1993) A novel G-protein coupled receptor kinase gene cloned from 4pl6.3.Human Nol. Gen. 1, 697–703.

    Article  Google Scholar 

  • Bahler M. and Greengard P. (1987) Synapsin I bundles F-actin in a phosphorylation-dependent manner.Nature 326, 704–707.

    Article  PubMed  CAS  Google Scholar 

  • Baines A. J. and Bennett V. (1986) Synapsin I is a microtubule-bundling protein.Nature 319, 145–147.

    Article  PubMed  CAS  Google Scholar 

  • Bear M. F. and Malenka R. C. (1994) Synaptic plasticity: LTP and LTD.Curr. Opi. Neurobiol. 4, 389–399.

    Article  CAS  Google Scholar 

  • Ben-Ari Y., Aniksztejn L., and Bregestovski P. (1992) Protein kinase C modulation of NMDA currents: an important link of LTP induction.Trends Neurosci. 15, 333–339.

    Article  PubMed  CAS  Google Scholar 

  • Benovic J. L. and Gomez J. (1993) Molecular cloning and expression of GRK6: a new member of the Gprotein-coupled receptor kinase family.J. Biol. Chem. 268, 19,521–19,527.

    CAS  Google Scholar 

  • Benovic J. L., Onorato J. J., Arriza J. L., Stone W. C., Lohse M., Jenkins N. A., Gilbert D. J., Copeland N. G., Caron M. G., and Lefkowitz R. J. (1991) Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family.J. Biol. Chem. 266, 14,939–14,946.

    CAS  Google Scholar 

  • Benowitz L. I. and Routtenberg A. (1997) GAP-43: an intrinsic determinant of neuronal development and plasticity.Trends Neurosci. 20, 84–91.

    Article  PubMed  CAS  Google Scholar 

  • Bito H., Deisseroth K., and Tsien R. W. (1996) CREB phosphorylation and dephosphorylation: a Ca2+- and stimulus duration-dependent switch for hippocampal gene expression.Cell 87, 1203–1214.

    Article  PubMed  CAS  Google Scholar 

  • Bonovic J. L., Mayor F. Jr., Staniszewski C., Lefkowitz R. J., and Caron M. G. (1987) Purification and characterization of the beta-adrenergic receptor kinase.J. Biol. Chem. 262, 9026–9032.

    Google Scholar 

  • Bosma M. M., Allen M. L., Martin T. M., and Tempel B. L. (1993) PKA-dependent regulation of mKv1.1, a mouse Shaker-like potassium channel gene, when stably expressed in CHO cells.J. Neurosci. 13, 5242–5250.

    PubMed  CAS  Google Scholar 

  • Boxall A. R., Lancaster B., and Garthwaite J. (1996) Tyrosine kinase is required for long-term depression in the cerebellum.Neuron 16, 805–813.

    Article  PubMed  CAS  Google Scholar 

  • Brandon E. P., Zhuo M., Huang Y. Y., Qi M., Gerhold K. A., Burton K. A., Kandel E. R., McKnight G. S., and Idzerda R. L.(1995) Hippocampal longterm depression and depotentiation are defective in mice carrying a targeted disruption of the gene encoding the RI beta subunit of cAMP-dependent protein kinase.Proc. Natl. Acad. Sci. USA 92, 8851–8855.

    Article  PubMed  CAS  Google Scholar 

  • Bredt D. S., Ferris C. D., and Snyder S. H. (1992) Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites.J. Biol. Chem. 267, 10,976–10,981.

    CAS  Google Scholar 

  • Brodkey J. A., Gates M. A., Laywell E. D., and Steindler D. A. (1993) The complex nature of interactive neuroregeneration-related molecules.Exp. Neurol. 123, 251–270.

    Article  PubMed  CAS  Google Scholar 

  • Castillo P. E., Weisskopf M. G., and Nicoll R. A. (1994) The role of Ca2+ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation.Neuron. 12, 261–269.

    Article  PubMed  CAS  Google Scholar 

  • Chad J. E. and Eckert R. (1986) An enzymatic mechanism for calcium current inactivation in dialysedHelix neurones.J. Physiol. Lond. 378, 31–51.

    PubMed  CAS  Google Scholar 

  • Chen C. and Leonard J. P. (1996) Protein tyrosine kinase-mediated potentiation of currents from cloned NMDA receptors.J. Neurochem. 67, 194–200.

    Article  PubMed  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 

  • Chen T. C., Law B., Kondratyuk T., and Rossie S. (1995) Identification of soluble protein phosphatases that dephosphorylate voltage-sensitive sodium channels in rat brain.J. Biol. Chem. 270, 7750–7756.

    Article  PubMed  CAS  Google Scholar 

  • Coleman P. D., Rogers K. E., and Flood D. G. (1995) Neuronal plasticity in normal aging and Alzheimer’s disease: a proposed intercellular signal cascade. Molecular and Cellular mechanisms of neuronal plasticity in normal aging and Alzheimer’s disease, inProgress in Brain Research, vol 86 (Coleman P. D., Higgins G. A., and Phelps C. H., eds.), Elsevier, pp. 74–87.

  • Costa M. R. C., Casnellie J. E., and Catterall W. A. (1982) Selective phosphorylation of the alpha subunit of the sodium channel by cAMP-dependent protein kinase.J. Biol. Chem. 257, 7918–7921.

    PubMed  CAS  Google Scholar 

  • Cotman C. W., Geddes J. W., Ulas J., and Klein M. (1990) Plasticity of exitatory amino acid receptors: implications for aging and Alzheimer’s disease. Molecular and Cellular mechanisms of neuronal plasticity in normal aging and Alzheimer’s disease, inProgress in Brain Research, vol 86 (Coleman P. D., Higgins G. A., and Phelps C. H., eds.), Elsevier, pp. 55–73.

  • Dawson T. M., Steiner J. P., Dawson V. L., Dinerman J. L., Uhl G. R., and Snyder S. H. (1993) Immunosuppressant FK506 enhances phosphorylation of nitric oxide synthase and protects against glutamate neurotoxicity.Proc. Natl. Acad. Sci. USA 90, 9808–9812.

    Article  PubMed  CAS  Google Scholar 

  • Deisseroth K., Bito H., and Tsien R. W. (1996) Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity.Neuron 16, 89–101.

    Article  PubMed  CAS  Google Scholar 

  • DeRemer M. F., Saeli R. J., and Edelman A. M. (1992) Ca2+-calmodulin-dependent protein kinases Ia and Ib from rat brain I. Identification, purification, and structural comparisons.J. Biol Chem. 267, 13,460–13,465.

    CAS  Google Scholar 

  • deToledo-Morrell L., Geinisman Y., and Morrell F. (1988) Age-dependent alterations in hippocampal synaptic plasticity: relation to memory disorders.Neurobiol. Aging 9, 581–590.

    Article  PubMed  CAS  Google Scholar 

  • Devillers-Thiery A., Galzi J. Jl., Eisele J. L., Bertran S., Bertrand D., and Changeux J. P. (1993) Functional architecture of the nicotinic acetylcholine receptor: a prototype of ligand-gated ion channels.J. Membr. Biol 136, 97–112.

    Article  PubMed  CAS  Google Scholar 

  • Enslen H., Sun P., Brickey D., Soderling S. H., Klamo E., and Soderling T. R. (1994) Characterization of Ca2+/calmodulin-dependent protein kinase IV. Role in transcriptional regulation.J. Biol. Chem. 269, 15,520–15,527.

    CAS  Google Scholar 

  • Feigenspan A. and Bormann J. (1994) Modulation of GABAc receptors in rat retinal bipolar cells by protein kinaseC. J. Physiol. Lond. 481, 325–330.

    CAS  Google Scholar 

  • Fournier F., Bourinet E., Nargeot J., and Charnet P. (1993) Cyclic AMP-dependent regulation of Ptype calcium channels expressed inXenopus oocytes.Pflugers. Arch. 423, 173–180.

    Article  PubMed  CAS  Google Scholar 

  • Fukunaga K., Muller D., and Miyamoto E. (1995) Increased phosphorylation of Ca2+/calmodulindependent protein kinase II and its endogenous substrates in the induction of long-term potentiation.J. Biol. Chem. 270, 6119–6124.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Funauchi M., Haruta H., and Tsumoto T. (1994) Effects of an inhibitor for calcium/calmodulindependent protein phosphatase, calcineurin, on induction of long-term potentiation in rat visual cortex.Neurosci. Res. 19, 269–278.

    Article  PubMed  CAS  Google Scholar 

  • Furukawa Y., Kim H. N., and Kubo T. (1995) Upand down-modulation of a clonedAplysia K+ channel (AKv1.la) by the activators of protein kinaseC. Zoolog. Sci. 12, 35–44.

    CAS  Google Scholar 

  • Friedlander M. J., Harsanyi K., Dudek S., and Kara P. (1996) Developmental mechanisms for regulating signal amplification at exitatory synapses in the neocortex. Neural development and plasticity, inProgress in Brain Research, vol 108 (Mize R. R. and Erzurumlu R. S., eds.), Elsevier, pp. 245–262.

  • Fykse E. M., Li C., and Sudhof T. C. (1995) Phosphorylation of rabphilin-3A by Ca2+/calmodulinand cAMP-dependent protein kinasesin vitro.J. Neurosci. 15, 2385–2395.

    PubMed  CAS  Google Scholar 

  • Gasic G. P. and Hollmann M. A. (1992) Molecular neurobiology of glutamate receptors.Ann. Rev. Physiol. 54, 507–536

    Article  CAS  Google Scholar 

  • Gianotti C., Nunzi M. G., Gispen W. H., and Corradetti R. (1992) Phosphorylation of the presynaptic protein B-50 (GAP-43) is increased during electrically induced long-term potentiation.Neuron 8, 843–848.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez G. A. and Montminy M. R. (1989) Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.Cell 59, 675–680.

    Article  PubMed  CAS  Google Scholar 

  • Grant S. G., O’Dell T. J., Karl K. A., Stein P. L., Soriano P., and Kandel E. R. (1992) Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.Science 258, 1903–1910.

    Article  PubMed  CAS  Google Scholar 

  • Grant S. G. and Silva A. J. (1994) Targeting learning.Trends Neurosci. 17, 71–75.

    Article  PubMed  CAS  Google Scholar 

  • Greengard P., Valtorta F., Czernik A. J., and Benfenati F. (1993) Synaptic vesicle phosphoproteins and regulation of synaptic function.Science 259, 780–785.

    Article  PubMed  CAS  Google Scholar 

  • Guy H. R. and Conti F. (1990) Pursuing the structure and function of voltage-gated channels.Trends Neurosci 13, 201–206.

    Article  PubMed  CAS  Google Scholar 

  • Haga K., Kameyama K., Haga T., Kikkawa U., Shiozaki K., and Uchiyama H. (1996) Phosphorylation of human ml muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinaseC. J. Biol. Chem. 271, 2776–2782.

    Article  CAS  Google Scholar 

  • Hell J. W., Yokoyama C. T., Wong S. T., Warner C., Snutch T. P., and Catterall W. A. (1993) Differential phosphorylation of two size forms of the neuronal class C L-type calcium channel alpha 1 subunit.J. Biol. Chem. 268, 19,451–19,457.

    CAS  Google Scholar 

  • Hell J. W., Appleyard S. M., Yokoyama C. T., Warner C., and Catterall W. A. (1994) Differential phosphorylation of two size forms of the N-type calcium channel alpha 1 subunit which have different COOH termini.J. Biol. Chem. 269, 7390–7396.

    PubMed  CAS  Google Scholar 

  • Hodgkiss J. P. and Kelly J. S. (1995a) Only ‘de novo’ long-term depression (LTD) in the rat hippocampus in vitro is blocked by the same low concentration of FK506 that blocks LTD in the visual cortex.Brain Res. 705, 241–246.

    Article  PubMed  CAS  Google Scholar 

  • Hodgkiss J. P. and Kelly J. S. (1995b) Only ‘de novo’ long-term depression (LTD) in the rat hippocampus in vitro is blocked by the same low concentration of FK506 that blocks LTD in the visual cortex.Brain Res. 705, 241–246.

    Article  PubMed  CAS  Google Scholar 

  • Huang X. Y., Morielli A. D., and Peralta E. G. (1993) Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor.Cell 75, 1145–1156.

    Article  PubMed  CAS  Google Scholar 

  • Huang Y. Y., Li X. C., and Kandel E. R. (1994) cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase.Cell 79, 69–79.

    Article  PubMed  CAS  Google Scholar 

  • Hvalby ^OO., Hemmings Jr. H. C., Paulsen O., Czernik A. J., Nairn A. C., Godfraind J-M., Jensen V., Raastad M., Storm J. F., Andersen P., and Greengard P. (1994) Specificity of protein kinase inhibito peptides and induction of long-term potentiation.Proc. Natl. Acad. Sci. USA 91, 4761–4765.

    Article  PubMed  CAS  Google Scholar 

  • Ikegami S., Kato A., Kudo Y., Kuno T., Ozawa F., and Inokuchi K. (1996) A facilitatory effect on the induction of long-term potentiationin vivo by chronic administration of antisense oligodeoxynucleotides against catalytic subunits of calcineurin.Brain Res. Mol. Brain Res. 41, 183–191.

    Article  PubMed  CAS  Google Scholar 

  • Jaffrey S. R. and Snyder S. H. (1995) Nitric oxide: a neural messenger.Ann. Rev. Cell. Dev. Biol. 11, 417–440.

    Article  CAS  Google Scholar 

  • Kano M., Kano M., Fukunaga K., and Konnerth A. (1996) Ca2+-induced rebound potentiation of gamma-aminobutyric acid-mediated currents requires activation of Ca2+/calmodulin-dependent kinase II.Proc. Natl. Acad. Sci. USA 93, 13351–13356.

    Article  PubMed  CAS  Google Scholar 

  • Kawabata S., Tsutsumi R., Kohara A., Yamaguchi T., Nakanishi S., and Okada M. (1996) Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors.Nature 383, 89–92.

    Article  PubMed  CAS  Google Scholar 

  • Kellenberger S., Malherbe P., and Sigel E. (1992) Function of the alpha 1 beta 2 gamma 2S gammaaminobutyric acid type A receptor is modulated by protein kinase C via multiple phosphorylation sites.J. Biol. Chem. 267, 25,660–25,663.

    CAS  Google Scholar 

  • Kolaj M., Cerne R., Cheng G., Brickey D. A., and Randic M. (1994) Alpha subunit 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 

  • Krishek B. J., Xie X., Blackstone C., Huganir R. L., Moss S. J., and Smart T. G. (1994) Regulation of GABAa receptor function by protein kinase C phosphorylation.Neuron 12, 1081–1095.

    Article  PubMed  CAS  Google Scholar 

  • Kuhn H. (1978) Light-dependent binding of rhodopsin kinase and other proteins to cattle photoreceptor membranes.Biochemistry 17, 4389–4395.

    Article  PubMed  CAS  Google Scholar 

  • Kunapuli P. and Benovic J. L. (1993) Cloning and expression of GRK5: a member of the G-proteincoupled receptor kinase family.Proc. Natl. Acad. Sci. USA 90, 5588–5592.

    Article  PubMed  CAS  Google Scholar 

  • Kusama T., Sakurai M., Kizawa Y., Uhl G. R., and Murakami H. (1995) GABA rho1 receptor: inhibition by protein kinase C activators.Eur. J. Pharmacol. 291, 431–434.

    Article  PubMed  CAS  Google Scholar 

  • Lai Y., Peterson B. Z., and Catterall W. A. (1993) Selective dephosphorylation of the subunits of skeletal muscle calcium channels by purified phosphoprotein phosphatases.J. Neurochem. 61, 1333–1339.

    Article  PubMed  CAS  Google Scholar 

  • Leidenheimer N. J. (1996) Effect of PKG activation on recombinant GABAa receptors.Brain. Res. Mol. Brain. Res. 42, 131–134.

    Article  PubMed  CAS  Google Scholar 

  • Leidenheimer N. J., McQuilkin S. J., Hahner L. D., Whiting P., and Harris R. A. (1992) Activation of protein kinase C selectively inhibits the gammaaminobutyric acid A receptor: role of desensitization.Mol. Pharmacol. 41, 1116–1123.

    PubMed  CAS  Google Scholar 

  • Lefkowitz R. J. (1993) G-protein-coupled receptor kinases.Cell 74, 409–412.

    Article  PubMed  CAS  Google Scholar 

  • Levitan I. B. (1994) Modulation of ion channels by protein phosphorylation and dephosphorylation.Ann. Rev. Physiol. 56, 193–212.

    Article  CAS  Google Scholar 

  • Lin Y. F., Browning M. D., Dudek E. M., and Macdonald R. L. (1994) Protein kinase C enhances recombinant bovine alpha 1 beta 1 gamma 2L GABAa receptor whole-cell currents expressed in L929 fibroblasts.Neuron 13, 1421–1431.

    Article  PubMed  CAS  Google Scholar 

  • Linden D. J. and Connor J. A. (1991) Participation of postsynaptic PKC in cerebellar long-term depression in culture.Science 254, 1656–1659.

    Article  PubMed  CAS  Google Scholar 

  • Lisman J. E. and Goldring M. A. (1988) Feasibility of long-term storage of graded information by the Ca2+/calmodulin-dependent protein kinase molecules of the postsynaptic density.Proc. Natl. Acad. Sci. USA 85, 5320–5324.

    Article  PubMed  CAS  Google Scholar 

  • Lu Y.-F., Tomizawa K., Moriwaki A., Hayashi Y., Tokuda M., Itano T., Hatase O., and Matsui H. (1996) Calcineurin inhibitors, FK506 and cyclosporin A, suppress the NMDA receptormediated potentials and LTP, but not depotentiation in the rat hippocampus.Brain Res. 729, 142–146.

    Article  PubMed  CAS  Google Scholar 

  • Lynch M. A. and Voss K. L. (1991) Presynaptic changes in long-term potentiation: elevated synaptosomal calcium concentration and basal phosphoinositide turnover in dentate gyrus.J. Neurochem. 56, 113–118.

    Article  PubMed  CAS  Google Scholar 

  • Machu T. K., Firestone J. A., and Browning M. D. (1993) Ca2+/calmodulin-dependent protein kinase II and protein kinase C phosphorylate a synthetic peptide corresponding to a sequence that is specific for the gamma 2L subunit of the GABAa receptor.J. Neurochem. 61, 375–377.

    Article  PubMed  CAS  Google Scholar 

  • Malenka R. C. and Nicoll R. A. (1993) NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms.Trends Neurosci. 16, 521–527.

    Article  PubMed  CAS  Google Scholar 

  • Malenka R. C. (1994) Synaptic plasticity in the hippocampus: LTP and LTD.Cell 78, 535–538.

    Article  PubMed  CAS  Google Scholar 

  • Martina M., Mozrzymas J. W., Boddeke H. W., and Cherubini E. (1996) The calcineurin inhibitor cyclosporin A-cyclophilin A complex reduces desensitization of GABAa-mediated responses in acutely dissociated rat hippocampal neurons.Neurosci. Lett. 215, 95–98.

    PubMed  CAS  Google Scholar 

  • Matsubara M., Kusubata M., Ishiguro K., Uchida T., Titani K., and Taniguchi H. (1996) Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions.J. Biol. Chem. 271, 21,108–21,113.

    CAS  Google Scholar 

  • McDonald B. J. and Moss S. J. (1994) Differential phosphorylation of intracellular domains of gamma-aminobutyric acid type A receptor subunits by calcium/calmodulin type 2-dependent protein kinase and cGMP-dependent protein kinase.J. Biol. Chem. 269, 18111–18117.

    PubMed  CAS  Google Scholar 

  • Moon I. S., Apperson M. L., and Kennedy M. B. (1994) The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B.Proc. Natl. Acad. Sci. USA 91, 3954–3958.

    Article  PubMed  CAS  Google Scholar 

  • Moss S. J., Doherty C. A., and Huganir R. L. (1992) Identification of the cAMP-dependent protein kinase and protein kinase C phosphorylation sites within the major intracellular domains of the beta 1, gamma 2S, and gamma 2L subunits of the gamma-aminobutyric acid type A receptor.J. Biol. Chem. 267, 14,470–14,476.

    CAS  Google Scholar 

  • Moss S. J., Gorrie G. H., Amato A., and Smart T. G. (1995) Modulation of GABAa receptors by tyrosine phosphorylation.Nature 377, 344–348.

    Article  PubMed  CAS  Google Scholar 

  • Muller D., Buchs P. A., Stoppini L., and Boddeke H. (1991) Long-term potentiation, protein kinase C, and glutamate receptors.Mol. Neurobiol. 5, 277–288.

    Article  PubMed  CAS  Google Scholar 

  • Mulkey R. M., Endo S., Shenolikar S., and Malenka R. C. (1994) Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression.Nature 369, 486–488.

    Article  PubMed  CAS  Google Scholar 

  • Mulkey R. M., Herron C. E., and Malenka R. C. (1993) An essential role for protein phosphatases in hippocampal long-term depression.Science 261, 1051–1055.

    Article  PubMed  CAS  Google Scholar 

  • Murphy B. J., Rogers J., Perdichizzi A. P., Colvin A. A., and Catterall W. A. (1996) cAMP-dependent phosphorylation of two sites in the alpha subunit of the cardiac sodium channel.J. Biol. Chem. 271, 28,837–28,843.

    CAS  Google Scholar 

  • Nicoll R. A., and Malenka R. C. (1995) Contrasting properties of two forms of long-term potentiatio in the hippocampus.Nature 377, 115–118.

    Article  PubMed  CAS  Google Scholar 

  • Numann R., Catterall W. A., and Scheuer T. (1991) Functional modulation of brain sodium channels by protein kinase C phosphorylation.Science 254, 115–118.

    Article  PubMed  CAS  Google Scholar 

  • O’Dell T. J., Kandel E. R., and Grant S. G. (1991) Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors.Nature 353, 558–560.

    Article  PubMed  CAS  Google Scholar 

  • O’Leary D. D., Ruff N. L., and Dyck R. H. (1994) Development, critical period plasticity, and adult reorganizations of mammalian somatosensory systems.Curr. Opinion Neurobiol. 4, 535–544.

    Article  CAS  Google Scholar 

  • Omkumar R. V., Kiely M. J., Rosenstein A. J., Min K. T., and Kennedy M. B. (1996) Identification of a phosphorylation site for calcium/calmodulindependent protein kinase II in the NR2.B subunit of the N-methyl-D-aspartate receptor.J. Biol. Chem. 271, 31670–31678.

    Article  PubMed  CAS  Google Scholar 

  • Pasinelli P., Ramakers G. M., Urban I. J., Hens J. J., Oestreicher A. B., de Graan P. N., and Gispen W. H. (1995) Long-term potentiation and synaptic protein phosphorylation.Behav. Brain. Res. 66, 53–59.

    Article  PubMed  CAS  Google Scholar 

  • Pedarzani P. and Storm J. F. (1994) PKA mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons.Neuron 11, 1023–1035.

    Article  Google Scholar 

  • Petrucci T. C. and Morrow J. S. (1987) Synapsin I: an actin-bundling protein under phosphorylation control.J. Cell. Biol. 105, 1355–1363.

    Article  PubMed  CAS  Google Scholar 

  • Popoli M. (1993) Synaptotagmin is endogenously phosphorylated by Ca2+/calmodulin protein kinase II in synaptic vesicles.FEBS Lett. 317, 85–88.

    Article  PubMed  CAS  Google Scholar 

  • Qi M., Zhuo M., Skalhegg B. S., Brandon E. P., Kandel E. R., McKnight G. S., and Idzerda R. L. (1996) Impaired hippocampal plasticity in mice lacking the Cbetal catalytic subunit of cAMP-dependent protein kinase.Proc. Natl. Acad. Sci. USA 93, 1571–1576.

    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 

  • Rosenbaum L. C., Malencik D. A., Anderson S. R., Tota M. R., and Schimerlik M. I. (1987) Phosphorylation of the porcine atrial muscarinic acetylcholine receptor by cyclic AMP dependent protein kinase.Biochemistry 26, 8183–8188.

    Article  PubMed  CAS  Google Scholar 

  • Rostas J. A., Brent V. A., Voss K., Errington M. L., Bliss T. V., and Gurd J. W. (1996) Enhanced tyrosine phosphorylation of the 2B subunit of the N-methyl-D-aspartate receptor in long-term potentiation.Proc. Natl. Acad. Sci. USA 93, 10,452–10,456.

    Article  CAS  Google Scholar 

  • Ruiz-Gomez A., Vaello M. L., Valdivieso F., and Mayor F. Jr. (1991) Phosphorylation of the 48-kDa subunit of the glycine receptor by protein kinaseC. J. Biol. Chem. 266, 559–566.

    CAS  Google Scholar 

  • Scheetz A. J. and Constantine-Paton M. (1994) Modulation of NMDA receptor function: implications for vertebrate neural development.FASEB J. 8, 745–752.

    PubMed  CAS  Google Scholar 

  • Severin S. E. Jr., Moskvitina E. L., Bykova E. V., Lutzenko S. V., and Shvets V. I. (1989) Synapsin I from human brain. Phosphorylation by Ca2+, phospholipid-dependent protein kinase.FEBS Lett. 258, 223–226.

    Article  PubMed  CAS  Google Scholar 

  • Sheng M., Thompson M. A., and Greenberg M. E. (1991) CREB: a Ca2+-regulated transcription factor phosphorylated by calmodulin-dependent kinases.Science 252, 1427–1430.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Silva A. J., Paylor R., Wehner J. M., and Tonegawa S. (1992b) Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice.Science 257, 206–211.

    Article  PubMed  CAS  Google Scholar 

  • Smith R. D. and Goldin A. L. (1992) Protein kinase A phosphorylation enhances sodium channel currents in Xenopus oocytes.Am. J. Physiol. 263, C660-C666.

    PubMed  CAS  Google Scholar 

  • Soderling T. R. (1993) Calcium/calmodulin-dependent protein kinase II: role in learning and memory.Mol. Cell Biochem. 127-128, 93–101.

    Article  PubMed  CAS  Google Scholar 

  • Son H., and Carpenter D. O. (1996) Protein kinase C activation is necessary but not sufficient for induction of long-term potentiation at the synapse of mossy fiber-CA3 in the rat hippocampus.Neuroscience 72, 1–13.

    Article  PubMed  CAS  Google Scholar 

  • Son H., Davis P. J., and Carpenter D. O. (1997) Time course and involvement of protein kinase C-mediated phosphorylation of F1/GAP-43 in area CA3 after mossy fiber stimulation.Cell. Mol. Neurobiol. 17, 171–94.

    Article  PubMed  CAS  Google Scholar 

  • Spear P. F. (1996) Neural plasticity after brain damage. Neural development and plasticity, inProgress in Brain Research, vol 108 (Mize R. R. and Erzurumlu R. S., eds.), Elsevier, pp. 391–408.

  • Stanton P. K. and Gage A. T. (1996) Distinct synaptic loci of Ca2+/calmodulin-dependent protein kinase II necessary for long-term potentiation and depression.J. Neurophysiol. 76, 2097–2101.

    PubMed  CAS  Google Scholar 

  • Stanton P. K. (1995) Transient protein kinase C activation primes long-term depression and suppresses long-term potentiation of synaptic transmission in hippocampus.Proc. Natl. Acad. Sci. USA 92, 1724–1728.

    Article  PubMed  CAS  Google Scholar 

  • Stuhmer W. (1991) Structure-function studies of voltage-gated ion channels.Annu. Rev. Biophys. Biophys. Chem. 20, 65–78.

    Article  PubMed  CAS  Google Scholar 

  • Sun P., Enslen H., Myung P. S., and Maurer R. A. (1994) Differential activation of CREB by Ca2+/ calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity.Genes Dev. 8, 2527–2539.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T. and Okumura-Noji K. (1995) NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain.Biochem. Biophys. Res. Commun. 216, 582–588.

    Article  PubMed  CAS  Google Scholar 

  • Timpe L. C., Schwarz T. L., Tempel B. L., Papazian D. M., Jan Y. N., and Jan L. Y. (1988) Expression of functional potassium channels from Shaker cDNA inXenopus oocytes.Nature 331, 143–145.

    Article  PubMed  CAS  Google Scholar 

  • Tokuda M., Ahmed B. Y., Lu Y.-F., Matsui H., Miyamoto O., Yamaguchi F., Konishi R., and Hatase O. (1997) Involvement of calmodulindependent protein kinases I and IV in long term potentiation.Brain Res. 755, 162–166.

    Article  PubMed  CAS  Google Scholar 

  • Tong G., Shepherd D., and Jahr C. E. (1995) Synaptic desensitization of NMDA receptors by calcineurin.Science 267, 1510–1512.

    Article  PubMed  CAS  Google Scholar 

  • Torii N., Kamishita T., Otsu Y., and Tsumoto T. (1995) An inhibitor for calcineurin, FK506, blocks induction of long-term depression in rat visual cortex.Neurosci. Lett. 185, 1–4.

    Article  PubMed  CAS  Google Scholar 

  • Vaello M. L., Ruiz-Gomez A., Lerma J., and Mayor F. Jr. (1994) Modulation of inhibitory glycine receptors by phosphorylation by protein kinase C and cAMP-dependent protein kinase.J. Biol. Chem. 269, 2002–2008.

    PubMed  CAS  Google Scholar 

  • Wadzinski B. E., Wheat W. H., Jaspers S., Peruski L. F. Jr., Lickteig R. L., Johnson G. L., and Klemm D. J. (1993) Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation.Mol. Cell Biol. 13, 2822–2834.

    PubMed  CAS  Google Scholar 

  • Wang J. H. and Stelzer A. (1994) Inhibition of phosphatase 2B prevents expression of hippocampal long-term potentiation.NeuroReport 5, 2377–2380.

    Article  PubMed  CAS  Google Scholar 

  • Wang L. Y., Orser B. A., Brautigan D. L., and MacDonald J. F. (1994) Regulation of NMDA receptors in cultured hippocampal neurons by protein phosphatases 1 and 2A.Nature 369, 230–232.

    Article  PubMed  CAS  Google Scholar 

  • Wang Y. T. and Salter M. W.(1994) Regulation of NMDA receptors by tyrosine kinases and phosphatases.Nature 369, 233–235.

    Article  PubMed  CAS  Google Scholar 

  • Wang Y. T., Yu X. M., and Salter M. W. (1996) Ca(2+)-independent reduction of N-methyl-D-aspartate channel activity by protein tyrosine phosphatase.Proc. Natl. Acad. Sci. USA 93, 1721–1725.

    Article  PubMed  CAS  Google Scholar 

  • Weisskopf M. G., Castillo P. E., Zalutsky R. A. and Nicoll R. A. (1994) Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP.Science 265, 1878–1882.

    Article  PubMed  CAS  Google Scholar 

  • West J. W., Numann R., Murphy B. J., Scheuer T., and Catterall W. A. (1991) A phosphorylation site in the Na+ channel required for modulation by protein kinase C.Science 254, 866–868.

    Article  PubMed  CAS  Google Scholar 

  • Yakel J. L. (1997) Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription.Trends Pharmacol. Sci. 18, 124–134.

    Article  PubMed  CAS  Google Scholar 

  • Yakel J. L., Vissavajjhala 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 

  • Yin J. C., Del-Vecchio M., Zhou H., and Tully T. (1995) CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila.Cell 81, 107–115.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Physiology, Kagawa Medical University, 1750-1 Ikenobe, Mikicho, 761-07, Kagawa, Japan

    Masaaki Tokuda & Osamu Hatase

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  1. Masaaki Tokuda
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Tokuda, M., Hatase, O. Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation. Mol Neurobiol 17, 137–156 (1998). https://doi.org/10.1007/BF02802028

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