Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II

Nature. 1993 Apr 15;362(6421):640-2. doi: 10.1038/362640a0.


The major postsynaptic density (PSD) protein at glutaminergic synapses is calcium/calmodulin-dependent protein kinase II (CaM-K II), but its function in the PSD is not known. We have examined glutamate receptors (GluRs) as substrates for CaM-K II because (1) they are colocalized in the PSD, (2) cloned GluRs contain consensus phosphorylation sites for protein kinases including CaM-K II, and (3) several GluRs are regulated by other protein kinases. Regulation of GluRs, which are involved in excitatory synaptic transmission and in mechanisms of learning and memory, by CaM-K II is of interest because of the postulated role of CaM-K II in synaptic plasticity and its known involvement in induction of long-term potentiation. Furthermore, mice lacking the major neural isoform of CaM-K II exhibit deficits in models of learning and memory that require hippocampal input. We report here that CaM-K II phosphorylates GluR in several in vitro systems, including the PSD, and that activated CaM-K II enhances kainate-induced ion current three- to fourfold in cultured hippocampal neurons. These results are consistent with a role for PSD CaM-K II in strengthening postsynaptic GluR responses in synaptic plasticity.

Publication types

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

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Cells, Cultured
  • Cloning, Molecular
  • Hippocampus / cytology
  • Moths
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Rats
  • Receptors, Glutamate / metabolism*


  • Nerve Tissue Proteins
  • Receptors, Glutamate
  • postsynaptic density proteins
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases