Interaction with the NMDA receptor locks CaMKII in an active conformation

K. Ulrich Bayer, Paul De Koninck, A. Soren Leonard, Johannes W Hell, Howard Schulman

Research output: Contribution to journalArticle

497 Citations (Scopus)

Abstract

Calcium- and calmodulin-dependent protein kinase II (CaMKII) and glutamate receptors are integrally involved in forms of synaptic plasticity that may underlie learning and memory. In the simplest model for long-term potentiation, CaMKII is activated by Ca2+ influx through NMDA (N-methyl-D-aspartate) receptors and then potentiates synaptic efficacy by inducing synaptic insertion and increased single-channel conductance of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Here we show that regulated CaMKII interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism for the glutamate-induced translocation of the kinase to the synapse in hippocampal neurons. This interaction can lead to additional forms of potentiation by: facilitated CaMKII response to synaptoc Ca2+; suppression of inhibitory autophosphorylation of CaMKII; and, most notably, direct generation of sustained Ca2+/calmodulin (CaM)-independent (autonomous) kinase activity by a mechanism that is independent of the phosphorylation state. Furthermore, the interaction leads to trapping of CaM that may reduce down-regulation of NMDA receptor activity. CaMKII-NR2B interaction may be prototypical for direct activation of a kinase by its targeting protein.

Original languageEnglish (US)
Pages (from-to)801-805
Number of pages5
JournalNature
Volume411
Issue number6839
DOIs
StatePublished - Jun 14 2001
Externally publishedYes

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
N-Methyl-D-Aspartate Receptors
Phosphotransferases
Calmodulin
Isoxazoles
Calcium-Calmodulin-Dependent Protein Kinases
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neuronal Plasticity
Long-Term Potentiation
Glutamate Receptors
Protein Transport
Synapses
Glutamic Acid
Down-Regulation
Phosphorylation
Learning
Neurons

ASJC Scopus subject areas

  • General

Cite this

Bayer, K. U., De Koninck, P., Leonard, A. S., Hell, J. W., & Schulman, H. (2001). Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature, 411(6839), 801-805. https://doi.org/10.1038/35081080

Interaction with the NMDA receptor locks CaMKII in an active conformation. / Bayer, K. Ulrich; De Koninck, Paul; Leonard, A. Soren; Hell, Johannes W; Schulman, Howard.

In: Nature, Vol. 411, No. 6839, 14.06.2001, p. 801-805.

Research output: Contribution to journalArticle

Bayer, KU, De Koninck, P, Leonard, AS, Hell, JW & Schulman, H 2001, 'Interaction with the NMDA receptor locks CaMKII in an active conformation', Nature, vol. 411, no. 6839, pp. 801-805. https://doi.org/10.1038/35081080
Bayer KU, De Koninck P, Leonard AS, Hell JW, Schulman H. Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature. 2001 Jun 14;411(6839):801-805. https://doi.org/10.1038/35081080
Bayer, K. Ulrich ; De Koninck, Paul ; Leonard, A. Soren ; Hell, Johannes W ; Schulman, Howard. / Interaction with the NMDA receptor locks CaMKII in an active conformation. In: Nature. 2001 ; Vol. 411, No. 6839. pp. 801-805.
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