Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP.
Long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse involves interacting signaling components, including calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhibitor of protein phosphatase-1 (PP1), substituted for cAMP pathway activation in LTP. Stimulation that induced LTP triggered cAMP-dependent phosphorylation of endogenous inhibitor-1 and a decrease in PP1 activity. This stimulation also increased phosphorylation of CaMKII at Thr286 and Ca2+-independent CaMKII activity in a cAMP-dependent manner. The blockade of LTP by a CaMKII inhibitor was not overcome by thiophosphorylated inhibitor-1. Thus, the cAMP pathway uses PP1 to gate CaMKII signaling in LTP.
Blitzer
R D
RD
Bronx VA Medical Center and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. rb2@doc.mssm.edu
Connor
J H
JH
Brown
G P
GP
Wong
T
T
Shenolikar
S
S
Iyengar
R
R
Landau
E M
EM
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D017774:Long-Term Potentiation; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D013873:Thionucleotides; C021042:protein phosphatase inhibitor-1; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1