Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II.
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.
Vollum Institute, Oregon Health Sciences University, Portland 97201.
E
E
McGlade-McCulloh
H
H
Yamamoto
S E
SE
Tan
D A
DA
Brickey
T R
TR
Soderling
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006624:Hippocampus / Q000166:cytology; D009036:Moths; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; C033652:postsynaptic density proteins; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases