EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner

Dynamic regulation of the localization and function of NMDA receptors (NMDARs) is critical for synaptic development and function. The composition and localization of NMDAR subunits at synapses are tightly regulated and can influence the ability of individual synapses to undergo long-lasting changes...

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Bibliographic Details
Published in:The Journal of neuroscience 2011-04, Vol.31 (14), p.5353-5364
Main Authors: Nolt, Mark J, Lin, Ying, Hruska, Martin, Murphy, Jessica, Sheffler-Colins, Sean I, Kayser, Matthew S, Passer, Joel, Bennett, Michael V L, Zukin, R Suzanne, Dalva, Matthew B
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Animals, Newborn
Biotinylation - physiology
Cells, Cultured
Cerebral Cortex - cytology
Embryo, Mammalian
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Female
Green Fluorescent Proteins - genetics
Hippocampus - cytology
Humans
In Vitro Techniques
Male
Mice
Mice, Knockout
Neurons - cytology
Neurons - physiology
Patch-Clamp Techniques - methods
Protein Subunits - genetics
Protein Subunits - metabolism
Protein Transport - genetics
Rats
Receptors, Eph Family - deficiency
Receptors, Eph Family - genetics
Receptors, Eph Family - metabolism
Receptors, N-Methyl-D-Aspartate - physiology
RNA, Small Interfering - metabolism
Synapses - physiology
Synaptosomes - metabolism
Transfection - methods
Up-Regulation - genetics
Up-Regulation - physiology
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Summary:Dynamic regulation of the localization and function of NMDA receptors (NMDARs) is critical for synaptic development and function. The composition and localization of NMDAR subunits at synapses are tightly regulated and can influence the ability of individual synapses to undergo long-lasting changes in response to stimuli. Here, we examine mechanisms by which EphB2, a receptor tyrosine kinase that binds and phosphorylates NMDARs, controls NMDAR subunit localization and function at synapses. We find that, in mature neurons, EphB2 expression levels regulate the amount of NMDARs at synapses, and EphB activation decreases Ca(2+)-dependent desensitization of NR2B-containing NMDARs. EphBs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple EphB knock-out mice lacking EphB1-3 exhibit homeostatic upregulation of NMDAR surface expression and loss of proper targeting to synaptic sites. These findings demonstrate that, in the mature nervous system, EphBs are key regulators of the synaptic localization of NMDARs.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0282-11.2011