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- Title
EphB Controls NMDA Receptor Function and Synaptic Targeting in a Subunit-Specific Manner.
- Authors
Nolt, Mark J.; Ying Lin; Hruska, Martin; Murphy, Jessica; Sheffler-Colins, Sean I.; Kayser51, Matthew S.; Passer, Joel; Bennett, Michael V. L.; Zukin, R. Suzanne; Dalva, Matthew B.
- Abstract
Dynamic regulation of the localization and function ofNMDAreceptors (NMDARs) is critical for synaptic development and function. The composition and localization ofNMDARsubunits 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 ofNMDARsat synapses, and EphB activation decreases Ca2+-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.
- Subjects
PROTEIN-tyrosine kinases; METHYL aspartate; NEURAL receptors; SYNAPSES; NEURONS
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 14, p5353
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0282-11.2011