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Decreased Protein Phosphatase 2A Activity in Hippocampal Long‐Term Potentiation
Author(s) -
Fukunaga Kohji,
Muller Dominique,
Ohmitsu Masao,
Bakó Eva,
DePaoliRoach Anna A.,
Miyamoto Eishichi
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.740807.x
Subject(s) - phosphatase , long term potentiation , phosphorylation , protein phosphatase 2 , protein kinase a , protein phosphatase 1 , protein subunit , biology , immunoprecipitation , biochemistry , ltp induction , protein phosphorylation , microbiology and biotechnology , chemistry , receptor , gene
Using autophosphorylated Ca 2+ /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 Mg 2+ ‐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 32 P‐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.