title: EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Nolt
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.forename: Martin
authors.initials: M
authors.lastname: Hruska
authors.forename: Jessica
authors.initials: J
authors.lastname: Murphy
authors.forename: Sean I
authors.initials: SI
authors.lastname: Sheffler-Colins
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Kayser
authors.forename: Joel
authors.initials: J
authors.lastname: Passer
authors.forename: Michael V L
authors.initials: MV
authors.lastname: Bennett
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dalva
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019921:Biotinylation / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D036081:Receptors, Eph Family / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D036081:Receptors, Eph Family