A model of synaptic memory: A CaMKII/PP1 switch that
potentiates transmission by organizing an AMPA receptor anchoring assembly
Lisman JE, Zhabotinsky AM
NEURON
31 (2): 191-201 AUG 2 2001
Abstract:
Ca2+/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.