Increased Phosphorylation of Myelin Basic Protein During Hippocampal Long-Term Potentiation

Authors

  • Coleen M. Atkins,

    1. Division of Neuroscience, Baylor College of Medicine, Houston, Texas, U.S.A.
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  • Shu-Jen Chen,

    1. Division of Neuroscience, Baylor College of Medicine, Houston, Texas, U.S.A.
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    • The present address of Dr. S.-J. Chen is Department of Physiology, SUNY, Buffalo, NY 14051, U.S.A.

  • Eric Klann,

    1. Division of Neuroscience, Baylor College of Medicine, Houston, Texas, U.S.A.
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    • The present address of Dr. E. Klann is Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.

  • J. David Sweatt

    Corresponding author
    1. Division of Neuroscience, Baylor College of Medicine, Houston, Texas, U.S.A.
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Address correspondence and reprint requests to Dr. J. D. Sweatt at Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, U.S.A.

Abstract

Abstract: Hippocampal long-term potentiation (LTP) is a long-lasting and rapidly induced increase in synaptic strength. Previous experiments have determined that persistent activation of protein kinase C (PKC) contributes to the early maintenance phase of LTP (E-LTP). Using the back-phosphorylation method, we observed an increase in the phosphorylation of a 21-kDa PKC substrate, termed p21, 45 min after LTP was induced in the CA1 region of the hippocampus. p21 was found to have the same apparent molecular weight as the 18.5-kDa isoform of myelin basic protein (MBP) and was recognized by an antibody to MBP in western blotting and immunoprecipitation. Furthermore, p21 from control and potentiated hippocampal slices and purified MBP have identical phosphopeptide maps when back-phosphorylated and then digested with either endoproteinase Lys-C or endoproteinase Asp-N, suggesting that p21 and MBP are identical proteins. As there was no observed change in the amount of MBP in LTP, the increase in MBP phosphorylation during LTP cannot be explained by a change in the amount of protein. From these experiments, we conclude that the phosphorylation of the 18.5-kDa isoform of MBP is increased during E-LTP.

Abbreviations used: APV, 2-amino-5-phosphonovalerate; Asp-N, endoproteinase Asp-N; BSA, bovine serum albumin; fEPSP, field excitatory postsynaptic potential; H7, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine; LTP, long-term potentiation; E-LTP, early maintenance phase of LTP; Lys-C, endoproteinase Lys-C; MBP, myelin basic protein; NMDA, N-methyl-d-aspartate; PKC, protein kinase C; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

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