A Model of Synaptic Memory: A CaMKII/PP1 Switch that Potentiates Transmission by Organizing an AMPA Receptor Anchoring Assembly

Ca 2+/calmodulin-dependent protein kinase II (CaMKII) is localized in the postsynaptic density (PSD) and is necessary for LTP induction. Much has been learned about the autophosphorylation of CaMKII and its dephosphorylation by PSD protein phosphatase-1 (PP1). Here, we show how the CaMKII/PP1 system...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2001-08, Vol.31 (2), p.191-201
Main Authors: Lisman, John E, Zhabotinsky, Anatol M
Format: Article
Language:English
Subjects:
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Humans
Long-Term Potentiation
Mathematics
Models, Neurological
Phosphoprotein Phosphatases - metabolism
Phosphorylation
postsynaptic density
Protein Phosphatase 1
Receptors, AMPA - physiology
Synapses - physiology
Synaptic Transmission - physiology
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Summary:Ca 2+/calmodulin-dependent protein kinase II (CaMKII) is localized in the postsynaptic density (PSD) and is necessary for LTP induction. Much has been learned about the autophosphorylation of CaMKII and its dephosphorylation by PSD protein phosphatase-1 (PP1). Here, we show how the CaMKII/PP1 system could function as an energy-efficient, bistable switch that could be activated during LTP induction and remain active despite protein turnover. We also suggest how recently discovered binding interactions could provide a structural readout mechanism: the autophosphorylated state of CaMKII binds tightly to the NMDAR and forms, through CaMKII-actinin-actin-(4.1/SAP97) linkages, additional sites for anchoring AMPARs at synapses. The proposed model has substantial experimental support and elucidates principles by which a local protein complex could produce stable information storage and readout.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(01)00364-6