TY - JOUR
T1 - EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner
AU - Nolt, Mark J.
AU - Lin, Ying
AU - Hruska, Martin
AU - Murphy, Jessica
AU - Sheffler-Colins, Sean I.
AU - Kayser, Matthew S.
AU - Passer, Joel
AU - Bennett, Michael V.L.
AU - Zukin, R. Suzanne
AU - Dalva, Matthew B.
PY - 2011/4/6
Y1 - 2011/4/6
N2 - 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 NMDA Rs, controls NMDAR subunit localization and function at synapses. We find that, in mature neurons, EphB2 expression levels regulate the amount of NMDAR sat synapses, and Eph B activation decreases Ca2+-dependent desensitization of NR2B-containing NMDA Rs. Eph Bs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple Eph B knock-out mice lacking EphB1-3 exhibit homeostatic up regulation 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 NMDA Rs.
AB - 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 NMDA Rs, controls NMDAR subunit localization and function at synapses. We find that, in mature neurons, EphB2 expression levels regulate the amount of NMDAR sat synapses, and Eph B activation decreases Ca2+-dependent desensitization of NR2B-containing NMDA Rs. Eph Bs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple Eph B knock-out mice lacking EphB1-3 exhibit homeostatic up regulation 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 NMDA Rs.
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U2 - 10.1523/JNEUROSCI.0282-11.2011
DO - 10.1523/JNEUROSCI.0282-11.2011
M3 - Article
C2 - 21471370
AN - SCOPUS:79955712301
SN - 0270-6474
VL - 31
SP - 5353
EP - 5364
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 14
ER -