Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP

Science. 1998 Jun 19;280(5371):1940-2. doi: 10.1126/science.280.5371.1940.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carrier Proteins*
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism*
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Electric Stimulation
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins*
  • Long-Term Potentiation*
  • Male
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Phosphatase 1
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Synapses / metabolism*
  • Thionucleotides / pharmacology

Substances

  • Carrier Proteins
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • RNA-Binding Proteins
  • Thionucleotides
  • protein phosphatase inhibitor-1
  • adenosine-3',5'-cyclic phosphorothioate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1