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C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors

Steigerwald, Frank and Schulz, Torsten W. and Schenker, Leslie T. and Kennedy, Mary B. and Seeburg, Peter H. and Köhr, Georg (2000) C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors. Journal of Neuroscience, 20 (12). pp. 4573-4581. ISSN 0270-6474. PMCID PMC6772457. doi:10.1523/JNEUROSCI.20-12-04573.2000.

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NMDA receptors interact via the extended intracellular C-terminal domain of the NR2 subunits with constituents of the postsynaptic density for purposes of retention, clustering, and functional regulation at central excitatory synapses. To examine the role of the C-terminal domain of NR2A in the synaptic localization and function of NR2A-containing NMDA receptors in hippocampal Schaffer collateral–CA1 pyramidal cell synapses, we analyzed mice which express NR2A only in its C-terminally truncated form. In CA1 cell somata, the levels, activation, and deactivation kinetics of extrasynaptic NMDA receptor channels were comparable in wild-type and mutant NR2A^(ΔC/ΔC) mice. At CA1 cell synapses, however, the truncated receptors were less concentrated than their full-length counterparts, as indicated by immunodetection in cultured neurons, synaptosomes, and postsynaptic densities. In the mutant, the NMDA component of evoked EPSCs was reduced in a developmentally progressing manner and was even more reduced in miniature EPSCs (mEPSCs) elicited by spontaneous glutamate release. Moreover, pharmacologically isolated NMDA currents evoked by synaptic stimulation had longer latencies and displayed slower rise and decay times, even in the presence of an NR2B-specific antagonist. These data strongly suggest that the C-terminal domain of NR2A subunits is important for the precise synaptic arrangement of NMDA receptors.

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Kennedy, Mary B.0000-0003-1369-0525
Additional Information:© 2000 Society for Neuroscience. Received January 27, 2000. Revision received March 31, 2000. Accepted April 7, 2000. This work was supported in part by Deutsche Forschungsgemeinschaft Grant Ko 1064. We thank Pfizer, Inc. for the gift of CP-101,606, Annette Herold for technical assistance, Drs. Rolf Sprengel, Pavel Osten, and Michael Müller, and members of the Sakmann (Heidelberg, Germany) and D'Angelo (Pavia, Italy) laboratories for discussions and for critical reading of this manuscript.
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)KO 1064
Subject Keywords:immunocytochemistry; Western blotting; patch clamp; hippocampal culture and slice; mice expressing; c-terminally truncated NR2A subunits; nucleated patches; evoked EPSCs; miniature currents; NR2B-specific antagonists (CP-101,606)
Issue or Number:12
PubMed Central ID:PMC6772457
Record Number:CaltechAUTHORS:20120424-154214639
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Official Citation:C-Terminal Truncation of NR2A Subunits Impairs Synaptic But Not Extrasynaptic Localization of NMDA Receptors. Frank Steigerwald, Torsten W. Schulz, Leslie T. Schenker, Mary B. Kennedy, Peter H. Seeburg, Georg Köhr. Journal of Neuroscience 15 June 2000, 20 (12) 4573-4581; DOI: 10.1523/JNEUROSCI.20-12-04573.2000
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30320
Deposited By: Melanie Stefan
Deposited On:24 Apr 2012 23:26
Last Modified:09 Nov 2021 19:45

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