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

Robert D. Blitzer, John H. Connor, George P. Brown, Tony Wong, Shirish Shenolikar, Ravi Iyengar, Emmanuel M. Landau

Research output: Contribution to journalArticlepeer-review

364 Scopus citations

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.

Original languageEnglish
Pages (from-to)1940-1943
Number of pages4
JournalScience
Volume280
Issue number5371
DOIs
StatePublished - 19 Jun 1998

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