Decreased protein phosphatase 2A activity in hippocampal long-term potentiation

Kohji Fukunaga, Dominique Muller, Masao Ohmitsu, Eva Bakó, Anna A. DePaoli-Roach, Eishichi Miyamoto

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Using autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) as substrate, we now find that long-term potentian (LTP) induction and maintenance are also associated with a significant decrease in calyculin A-sensitive protein phosphatase (protein phosphatase 2A) activity, without changes in Mg2+dependent protein phosphatase (protein phosphatase 2C) activity. This decrease in protein phosphatase 2A activity was prevented when LTP induction was inhibited by treatment with calmidazolium or D-2- amino-5-phosphonopentanoic acid. In addition, the application of high- frequency stimulation to 32P-labeled hippocampal slices resulted in increases in the phosphorylation of a 55-kDa protein immunoprecipitated with anti-phosphatase 2A antibodies. Use of a specific antibody revealed that the 55-kDa protein is the B'α subunit of protein phosphatase 2A. Following purification of brain protein phosphatase 2A, the B'α subunit was phosphorylated by CaM kinase II, an event that led to the reduction of protein phosphatase 2A activity. These results suggest that the decreased activity in protein phosphatase 2A following LTP induction contributes to the maintenance of constitutively active CaM kinase II and to the long-lasting increase in phosphorylation of synaptic components implicated in LTP.

Original languageEnglish (US)
Pages (from-to)807-817
Number of pages11
JournalJournal of Neurochemistry
Volume74
Issue number2
DOIs
StatePublished - Jan 29 2000

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Keywords

  • Ca/calmodulin-dependent protein kinase II
  • Hippocampus
  • Long-term potentiation
  • Protein phosphatase 2A
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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