Gating of CaMKII by cAMP-Regulated Protein Phosphatase Activity During LTP

• DOI: 10.1126/science.280.5371.1940
• Publication Date: 2002-07-27T09:43:20Z
• Authors: Robert D. Blitzer; John H. Connor; George P. Brown; Tony Wong; Shirish Shenolikar; Ravi Iyengar; Emmanuel M. Landau
• Keywords: Male; 0301 basic medicine; Long-Term Potentiation; Intracellular Signaling Peptides and Proteins; RNA-Binding Proteins; In Vitro Techniques; Cyclic AMP-Dependent Protein Kinases; Hippocampus; Electric Stimulation; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Protein Phosphatase 1; Calcium-Calmodulin-Dependent Protein Kinases; Cyclic AMP; Phosphoprotein Phosphatases; Animals; Enzyme Inhibitors; Phosphorylation; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Carrier Proteins; Signal Transduction

Long-term potentiation (LTP) at the Schaffer collateral–CA1 synapse involves interacting signaling components, including calcium (Ca 2+ )/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 Thr 286 and Ca 2+ -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.