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

Nature volume 362, pages 640–642 (1993)Cite this article

Abstract

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 PSD3, (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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Authors and Affiliations

  1. Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97201, USA

    Ellen McGlade-McCulloh, Hideyuki Yamamoto, Soon-Eng Tan, Debra A. Brickey & Thomas R. Soderling

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  1. Ellen McGlade-McCulloh
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  2. Hideyuki Yamamoto
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McGlade-McCulloh, E., Yamamoto, H., Tan, SE. et al. Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II. Nature 362, 640–642 (1993). https://doi.org/10.1038/362640a0

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