TY - JOUR
T1 - Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II
AU - McGlade-Mcculloh, Ellen
AU - Yamamoto, Hideyuki
AU - Tan, Soon Eng
AU - Brickey, Debra A.
AU - Soderling, Thomas R.
PY - 1993
Y1 - 1993
N2 - The major postsynaptic density (PSD) protein1,2 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 3, (2) cloned GluRs4-7 contain consensus phosphorylation sites for protein kinases including CaM-K II, and (3) several GluRs are regulated by other protein kinases8-12. Regulation of GluRs, which are involved in excitatory synaptic transmission and in mechanisms of learning and memory13, by CaM-K II is of interest because of the postulated role of CaM-K II in synaptic plasticity14,15 and its known involvement in induction of long-term potentiation16. Furthermore, mice lacking the major neural isoform of CaM-K II exhibit deficits in models of learning and memory that require hippocampal input17,18. 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.
AB - The major postsynaptic density (PSD) protein1,2 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 3, (2) cloned GluRs4-7 contain consensus phosphorylation sites for protein kinases including CaM-K II, and (3) several GluRs are regulated by other protein kinases8-12. Regulation of GluRs, which are involved in excitatory synaptic transmission and in mechanisms of learning and memory13, by CaM-K II is of interest because of the postulated role of CaM-K II in synaptic plasticity14,15 and its known involvement in induction of long-term potentiation16. Furthermore, mice lacking the major neural isoform of CaM-K II exhibit deficits in models of learning and memory that require hippocampal input17,18. 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.
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U2 - 10.1038/362640a0
DO - 10.1038/362640a0
M3 - Article
C2 - 8385275
AN - SCOPUS:0027480086
SN - 0028-0836
VL - 362
SP - 640
EP - 642
JO - Nature
JF - Nature
IS - 6421
ER -