Abstract
Behaviorally active neuropeptides might affect synaptic plasticity by changing the degree of phosphorylation of synaptic proteins. Neuronal electrical activity and neurotransmission are accompanied by covalent modification of synaptic proteins through cyclic phosphorylation and dephosphorylation (c.f. Weller, 1979). Studies using behavioral paradigms similar to those used to measure the behavioral effects of melanocortins (ACTH/MSH) suggested that the acquisition of new information may be accompanied by changes in the degree of phosphorylation of synaptic phosphoproteins (Glassman et al., 1973). The original idea was to study the in vitro modulation of synaptic plasma membrane phosphorylation by ACTH1-24 and its behaviorally active fragments and to compare the structural requirements of ACTH in this assay with those influencing the extinction of active avoidance behavior (Greven and De Wied, 1973). In our first study along this line, we noted that high concentrations of ACTH1-24 indeed inhibited the endogenous phosphorylation of several phosphoproteins in rat brain synaptic membranes (Zwiers et al., 1976). These phosphoproteins were phosphorylated by a cyclic AMP-independent mechanism, at that time the most important phosphorylation system studied (Zwiers et al., 1976). Our next step was to investigate the nature of the affected substrate proteins and their corresponding kinase(s).
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References
Akers, R. F. and Routtenberg, A., Protein kinase C phosphorylates a 47 Mr protein (F1) directly related to synaptic plasticity, Brain Res. 334: 147–151 (1985).
Aloyo, V. J., Zwiers, H. and Gispen, W. H., B-50 protein kinase and kinase C in rat brain, Prog. Brain Res. 56: 303–315 (1982).
Aloyo, V. J., Zwiers, H. and Gispen, W. H., Phosphorylation of B-50 by calcium-activated phospholipid-dependent protein kinase and B-50 protein kinase, J. Neurochem. 41: 649–653 (1983).
Berridge, M. J. and Irvine, R. F., Inositol trisphosphate, a novel second messenger in cellular signal transduction, Nature (London) 312: 649–653 (1984).
Castagna, M., Takai, Y., Kaibuchi, K., Sano, U., Kikkawa, U. and Nishizuka, Y., Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol diesters, J. Biol. Chem. 257: 7847–7851 (1982).
De Graan, P. N. E., Van Hooff, C. O. M., Tilly, B. C., Oestreicher, A. B., Schotman, P. and Gispen, W. H., Phosphoprotein B-50 in nerve growth cones from fetal rat brain, Neurosci. Lett. 61: 235–241 (1985).
De Graan, P. N. E., Oestreicher, A. B., Schrama, L. H. and Gispen, W. H., Phosphoprotein B-50: localization and function, Prog. Brain. Res. 69: 37–50 (1986a).
De Graan, P. N. E., Schrama, L. H. and Gispen, W. H., Characterization of a 52 kDa phosphoprotein possibly related to long-term potentiation, in: “Proceedings VIIth International Neurobiological Symposium on Learning and Memory, Oct 28 — Nov 2 (1985), Magdeburg (GDR)”, Pergamon Press, Oxford, in press (1986b).
DeRiemer, S. A., Strong, J. A., Albert, K., Greengard, P. and Kaczmarek, L. K., Phorbol ester and protein kinase C enhance calcium current in Aplysia neurones, Nature (London) 313: 313–316 (1985a).
DeRiemer, S. A., Greengard, P. and Kaczmarek, L. K., Calcium/phosphatidylserine/diacylglycerol-dependent protein phosphorylation in the Alplysia nervous system, J. Neurosci. 5: 2672–2676 (1985b).
Di Virgilio, F., Pozzan, T., Wollheim, C. B., Vicentini, L. M. and Meldolesi, J., Tumor promoter phorbol myristate acetate inhibits Ca2+ influx through voltage-gated Ca2+ channels in two secretory cell lines, PC12 and RINm5F, J. Biol. Chem. 261: 32–35 (1986).
Dunkley, P. R. and Robinson, P. J., Depolarization-dependent protein phosphorylation in synaptosomes: mechanisms and significance, Prog. Brain Res. 69: 273–294 (1986).
Eichberg, J., De Graan, P. N. E., Schrama, L. H. and Gispen, W. H., Dioctanoylglycerol and phorbol esters enhance phosphorylation of phosphoprotein B-50 in native synaptic plasma membranes, Biochem. Biophys. Res. Commun. 136: 1007–1012 (1986).
Farese, R. V., Rosic, N., Babischkin, J., Farese, M. G., Foster, R. and Davis, J. S., Dual activation of the inositol-trisphosphate-calcium and cyclic nucleotide intracellular signaling systems by adrenocorticotropin in rat adrenal cells, Biochem. Biophys. Res. Commun. 135: 742–748 (1986).
Gispen, W. H., Wiegant, V. M., Greven, H. M. and De Wied, D., The induction of excessive grooming behavior in the rat by intracerebroventricular application of peptides derived from ACTH: structure-activity studies, Life Sci. 17: 645–652 (1975).
Gispen, W. H., Zwiers, H., Wiegant, V. M., Schotman, P. and Wilson, J. E., The behaviorally active neuropeptide ACTH as neurohormone and neuromodulator: the role of cyclic nucleotides and membrane phosphoproteins, Adv. Exp. Med. Biol. 116: 199–224 (1979).
Gispen, W. H. and Isaacson, R. L., ACTH-induced excessive grooming in the rat, Pharmacol. Ther. 12: 209–246 (1981).
Gispen, W. H., Van Dongen, C. J., De Graan, P. N. E., Oestreicher, A. B. and Zwiers, H., The role of phosphoprotein B-50 in phosphoinositide metabolism in brain synaptic plasma membranes, in: “Inositol and Phosphoinositides”, J. E. Bleasdale, G. Hauser, J. Eichberg, eds, Humana Press, Dallas (1985a).
Gispen, W. H., Leunissen, J. L. M., Oestreicher, A. B., Verkleij, A. J. and Zwiers, H., Presynaptic localization of B-50 phosphoprotein: the ACTH-sensitive protein kinase substrate involved in rat brain polyphosphoinositide metabolism, Brain Res. 328: 381–385 (1985b).
Gispen, W. H., Schrama, L. H. and Eichberg, J., Stimulation of protein kinase C reduces ACTH-induced excessive grooming, Eur. J. Pharmacol. 114: 399–400 (1985c).
Gispen, W. H., De Graan, P. N. E., Chan, S. Y. and Routtenberg, A., Comparison between the neural acidic proteins B-50 and F1, Prog. Brain Res. 69: in press (1986).
Glassman, E., Gispen, W. H., Perumal, R., Machlus, B. and Wilson, J. E., The effect of short experiences on the incorporation of radioactive phosphate into synaptosomal and non-histone acid-extractable nuclear proteins from rat and mouse brain, in: “Proceedings 5th International Congress Pharmacology”, San Francisco, Vol. 4 (1973).
Gower, H. and Rodnight, R., Intrinsic protein phosphorylation in synaptic plasma membrane fragments from the rat. General characteristics and migration behavior on Polyacrylamide gels of the main phosphate receptors, Biochim. Biophys. Acta 716: 45–52 (1982).
Gower, H., Rodnight, R. and Branimer, M. J., Ca2+-sensitivity of Ca2+-dependent protein kinase activities toward intrinsic proteins in synaptosomal membrane fragments from rat cerebral tissue, J. Neurochem. 46: 440–447 (1986).
Greven, H. M. and De Wied, D., The influence of peptides derived from corticotropin (ACTH) on performance. Structure-activity studies. Prog. Brain Res. 39: 429–442 (1973).
Isaacson, R. L., Hannigan, J. H., Brakkee, J. H. and Gispen, W. H., The time course of excessive grooming after neuropeptide administration, Brain. Res. Bull. 11: 289–293 (1983).
Jolles, J., Zwiers, H., Van Dongen, C. J., Schotman, P., Wirtz, K. W. A. and Gispen, W. H., Modulation of brain polyphosphoinositide metabolism by ACTH-sensitive protein phosphorylation, Nature 286: 623–625 (1980).
Jolles, J., Zwiers, H., Dekker, A., Wirtz, K. W. A. and Gispen, W. H., Corticotropin-(1-24)-tetracosapeptide affects protein phosphorylation and polyphosphoinositide metabolism in rat brain, Biochem. J. 194: 283–291 (1981).
Jork, R., De Graan, P. N. E., Van Dongen, C. J., Zwiers, H., Matthies, H. and Gispen, W. H., Dopamine-induced changes in protein phosphorylation and polyphosphoinositide metabolism in rat hippocampus, Brain Res. 291: 73–81 (1984).
Katz, F., Ellis, L. and Pfenninger, K. H., Nerve growth cones isolated from fetal rat brain, J. Neurosci. 5: 1402–1411 (1985).
Kikkawa, U., Takai, Y., Tanaka, R., Miyake, R. and Nishizuka, Y., Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters, J. Biol. Chem. 258: 11442–11445 (1983).
Kikkawa, U., Kitano, T., Saito, N., Fujiwara, H., Nakanishi, H., Kishimoto, A., Taniyama, K., Tanaka, C. and Nishizuka, Y., Possible roles of protein kinase C in signal transduction in nervous tissues, Prog. Brain Res. 69: 29–38 (1986).
Kristjansson, G. I., Zwiers, H., Oestreicher, A. B. and Gispen, W. H., Evidence that the synaptic phosphoprotein B-50 is localized exclusively in nerve tissue, J. Neurochem. 39: 371–378 (1982).
Labarca, R., Janowsky, A., Patel, J. and Paul, S. M., Phorbol esters inhibit agonist induced 3H-inositol-l-phosphate accumulation in rat hippocampal slices, Biochem. Biophys. Res. Commun. 123: 703–709 (1984).
Leeb-Lundberg, L. M. F., Cotecchia, S., Lomasney, J. W., DeBernardis, J. F., Lefkowitz, R. J., and Caron, M. G., 1985, Phorbol esters promote α-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism, Proc. Natl. Acad. Sci. USA 82: 5651–5655 (1985).
Mahler, H. R., Kleine, L. P., Ratner, N. and Sorensen, R. G., Identification and topography of synaptic phosphoproteins, Progr. Brain Res. 56: 27–48 (1982).
Niedel, J. E., Kuhn, L. J. and Vanderbark, G. R., Phorbol diester receptor copurifies with protein kinase C., Proc. Natl. Acad. Sci. USA 80: 36–40 (1983).
Nishizuka, Y., The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature (London) 308: 693–697 (1984).
Oestreicher, A. B., Zwiers, H., Schotman, P. and Gispen, W. H., Immunohistochemical localization of a phosphoprotein (B-50) isolated from rat brain synaptosomal plasma membranes, Brain Res. Bull. 6: 145–153 (1981).
Oestreicher, A. B., Van Dongen, A. B., Zwiers, H. and Gispen, W. H., Affinity-purified anti-B-50 protein antibody: interference with the function of the phosphoprotein B-50 in synaptic plasma membranes, J. Neurochem. 41: 331–340 (1983).
Oestreicher, A. B., Van Duin, M., Zwiers, H. and Gispen, W. H., Cross-reaction of anti-rat B-50: characterization and isolation of a ‘B-50-phosphoprotein’ from bovine brain, J. Neurochem. 43: 935–943 (1984).
Oestreicher, A. B., Dekker, L. V. and Gispen, W. H., A radioimmunoassay for the phosphoprotein B-50: distribution in rat brain, J. Neurochem. 46: 1366–1369 (1986).
Okano, Y., Takagi, H., Nakashima, S., Tohmatsu, T. and Nozawa, Y., Inhibitory action of phorbol myristate acetate on histamine secretion and polyphosphoinositide turnover induced by compound 48/80 in mast cells, Biochem. Biophys. Res. Commun. 132: 110–117 (1985).
Orella, S. A., Solski, P. A. and Brown, J. H., Phorbol ester inhibits phosphoinositide hydrolysis and calcium mobilization in cultured astrocytoma cells, J. Biol. Chem. 260: 5236–5239 (1985).
Rane, S. G. and Dunlap, K., Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons, Proc. Natl. Acad. Sci. USA 83: 184–188 (1986).
Rodnight, R., Aspects of protein phosphorylation in the nervous system with particular reference to synaptic transmission, Progr. Brain Res. 56: 1–25 (1982).
Routtenberg, A., Lovinger, D. M. and Steward, P., Selective increase in phosphorylation state of a 47 kDa protein (F1) directly related to longterm potentiation, Behav. Neural Biol. 43: 3–11 (1985).
Schrama, L. H., De Graan, P. N. E., Eichberg, J. and Gispen, W. H., Feedback control of the inositol phospholipid response in rat brain is sensitive to ACTH, Eur. J. Pharmacol. 121: 403–404 (1986a).
Schrama, L. H., De Graan, P. N. E., Wadman, W. J., Lopes da Silva, F. H. and Gispen, W. H., Long-term potentiation and 4-aminopyridine-induced changes in protein-and lipid-phosphorylation in the hippocampal slice, Prog. Brain Res. 69: in press (1986b).
Sorensen, R. G., Kleine, L. P. and Mahler, H. R., Presynaptic localization of phosphoprotein B-50, Brain Res. Bull. 7: 57–61 (1981).
Spruijt, B. M., Cools, A. R. and Gispen, W. H., The periaqueductal gray: a prerequisite for ACTH-induced excessive grooming, Behav. Brain Res. in press (1986).
Streb, H., Irvine, R. F., Berridge, M. J. and Schulz, I., Release of Ca2+ from a nonmitrochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate, Nature (London) 306: 67–69 (1983).
Takai, Y., Kishimoto, A., Kikkawa, U., Mori, T. and Nishizuka, Y., Unsaturated diacylglycerol as a possible messenger for the activation of calcium-activated, phospholipid-dependent protein kinase system, Biochem. Biophys. Res. Commun. 91: 1218–1224 (1979).
Takai, Y., Kaibuchi, K., Tsuda, T. and Hoshijima, M., Ro1e of protein kinase C in transmembrane signalling, J. Cell. Biochem. 29: 143–155 (1985).
Tohmatsu, T., Hattori, H., Nagao, S., Ohki, K. and Nozawa, Y., Reversal by protein kinase C inhibitor of suppressive actions of phorbol-12-myristate-13-acetate on polyphosphoinositide metabolism and cytosolic Ca2+ mobilization in trombin-stimulated human platelets, Biochem. Biophys. Res. Commun. 134: 868–875 (1986).
Van Dongen, C. J., Zwiers, H. and Gispen, W. H., Purification and partial characterization of the phosphatidylinositol 4-phosphate kinase from rat brain, Biochem. J. 223: 197–203 (1984).
Van Dongen, C. J., Zwiers, H., De Graan, P. N. E. and Gispen, W. H., Modulation of the activity of purified phosphatidylinositol 4-phosphate kinase by phosphorylated and dephosphorylated B-50, Biochem. Biophys. Res. Commun. 128: 1219–1227 (1985).
Van Dongen, C. J., Kok, J. W., Schrama, L. H., Oestreicher, A. B. and Gispen, W. H., Immunochemical characterization of phosphatidylinositol 4-phosphate kinase from rat brain, Biochem. J. 233: 859–864 (1986).
Vicentini, L. M., Di Virgilio, F., Ambrosini, A., Pozzan, T. and Meldolesi, J., Tumor promoter phorbol 12-myristate, 13-acetate inhibits phosphoinositide hydrolysis and cytosolic Ca2+ rise induced by the activation of muscarinic receptors in PC12 cells, Biochem. Biophys. Res. Commun. 127: 310–317 (1985).
Watson, S. J., Richard, C. W. III and Barchas, J. D., Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons, Science 275: 226–228 (1978).
Watson, S. P. and Lapetina, E. G., 1,2-Diacylglycerol and phorbol ester inhibit agonist-induced formation of inositol phosphates in human platelets: possible implications for negative feedback regulation of inositol phospholipid hydrolysis, Proc. Natl. Acad. Sci. USA 82: 2623–2626 (1985).
Weller, M., “Protein phosphorylation. The Nature, Function and Metabolism of Proteins, which Contain Covalently Bound Phosphorus”, PION Ltd, London (1979).
Worley, P. F., Barbaban, J. M. and Snyder, S. H., Heterogeneous localization of protein kinase C in rat brain: autoradiographic analysis of phorbol ester receptor binding, J. Neurosci. 6: 199–207 (1986).
Zwiers, H., Veldhuis, H. D., Schotman, P. and Gispen, W. H., ACTH, cyclic nucleotides, and brain protein phosphorylation in vitro, Neurochem. Res. 1: 669–677 (1976).
Zwiers, H., Wiegant, V. M., Schotman, P. and Gispen, W. H., Intraventricular administered ACTH and changes in rat brain phosphorylation: a preliminary report, in: “Mechanism, Regulation and Special Functions of Protein Synthesis in the Brain”, S. Roberts, A. Lajhta, and W. H. Gispen, eds. Elsevier/North-Holland Biomedical Press, Amsterdam (1977).
Zwiers, H., Wiegant, V. M., Schotman, P. and Gispen, W. H., ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: structure-activity, Neurochem. Res. 3: 247–256 (1978).
Zwiers, H., Tonnaer, J., Wiegant, V. M., Schotman, P. and Gispen, W. H., ACTH-sensitive protein kinase from rat brain membranes, J. Neurochem. 33: 247–256 (1979).
Zwiers, H., Schotman, P. and Gispen, W. H., Purification and some characteristics of an ACTH-sensitive protein kinase and its substrate protein in rat brain membrane, J. Neurochem. 34: 1689–1699 (1980).
Zwiers, H., Jolles, J., Aloyo, V. J., Oestreicher, A. B. and Gispen, W. H., ACTH and synaptic membrane phosphorylation in rat brain, Prog. Brain Res. 56: 405–417 (1982).
Zwiers, H., Verhaagen, J., Van Dongen, C. J., De Graan, P. N. E. and Gispen, W. H., Resolution of rat brain synaptic phosphoprotein B-50 into multiple forms by two-dimensional electrophoresis: evidence for multisite phosphorylation, J. Neurochem. 44: 1083–1090 (1985).
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Schrama, L.H., De Graan, P.N.E., Oestreicher, A.B., Gispen, W.H. (1987). B-50 Phosphorylation, Protein Kinase C and the Induction of Excessive Grooming Behavior in the Rat. In: Ehrlich, Y.H., Lenox, R.H., Kornecki, E., Berry, W.O. (eds) Molecular Mechanisms of Neuronal Responsiveness. Advances in Experimental Medicine and Biology, vol 221. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7618-7_29
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