Title | Interaction with the NMDA receptor locks CaMKII in an active conformation. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Bayer K U, De Koninck P, Leonard AS, Hell JW, Schulman H |
Journal | Nature |
Volume | 411 |
Issue | 6839 |
Pagination | 801-5 |
Date Published | 2001 Jun 14 |
ISSN | 0028-0836 |
Keywords | Animals, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinases, Calmodulin, Cell Line, Enzyme Activation, Hippocampus, Neurons, Phosphorylation, Protein Binding, Protein Conformation, Rats, Receptors, N-Methyl-D-Aspartate, Recombinant Fusion Proteins |
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 (alpha-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 synaptic 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. |
DOI | 10.1038/35081080 |
Alternate Journal | Nature |
PubMed ID | 11459059 |