Decreased protein phosphatase 2A activity in hippocampal long-term potentiation.
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'alpha subunit of protein phosphatase 2A. Following purification of brain protein phosphatase 2A, the B'alpha 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.
Fukunaga
K
K
Department of Pharmacology, Kumamoto University School of Medicine, Japan. fukunaga@gpo.kumamoto-u.ac.jp
Muller
D
D
Ohmitsu
M
M
Bakó
E
E
DePaoli-Roach
A A
AA
Miyamoto
E
E
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D051381:Rats; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts / Q000378:metabolism
D007527:Isoenzymes; D014020:Tissue Extracts; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2