A structural mechanism for maintaining the 'on-state' of the CaMKII memory switch in the post-synaptic density

J Neurochem. 2007 Oct;103(1):357-64. doi: 10.1111/j.1471-4159.2007.04744.x.


Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by Ca(2+) entry into neurons. Autophosphorylation of T286 is of special importance because it makes the enzyme active in the absence of Ca(2+), providing a biochemical memory that is critical for plasticity. To understand the factors controlling the duration of this state of CaMKII, we studied dephosphorylation of CaMKII in the post-synaptic density (PSD), a structure that defines a neuronal subcompartment critical for plasticity. We found that PSD-resident PP1 can dephosphorylate many sites on CaMKII, but not the T286 site that produces Ca(2+)-independent activity. This, together with previous work showing that soluble PP2A cannot dephosphorylate PSD CaMKII, provides a novel explanation for the in vivo persistence of T286 phosphorylation: after activated CaMKII translocates from the cytoplasm to the PSD, structural constraints prevent phosphatases from dephosphorylating T286. These results also suggest that the PSD is more than a simple scaffold for synaptic proteins; it may act to regulate the activity of proteins by positioning them in orientations that either prevent or favor specific biochemical reactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cerebral Cortex / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Learning / physiology
  • Long-Term Potentiation / physiology
  • Memory / physiology*
  • Phosphorylation
  • Protein Transport / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / chemistry
  • Synapses / metabolism*


  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases