
Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca2+/calmodulin-dependent protein kinase phosphorylates the tail domain of KIF17, a member of the kinesin superfamily, to control NMDA receptor subunit 2B (GluN2B) transport by changing the KIF17–cargo interactionin vitro. However, the mechanisms of regulation of GluN2B transportin vivoand its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 (TgS), or KIF17 with S1029A (TgA) or S1029D (TgD)phosphomimicmutations inkif17−/−background.TgA/kif17−/−andTgD/kif17−/−mice exhibited reductions in synaptic NMDA receptors because of their inability to load/unload GluN2B onto/from KIF17, leading to impaired neuronal plasticity, CREB activation, and spatial memory. Expression of GFP-KIF17 inTgS/kif17−/−mouse neurons rescued the synaptic and behavioral defects ofkif17−/−mice. These results suggest that phosphorylation-based regulation of NMDA receptor transport is critical for learning and memoryin vivo.
Male, Analysis of Variance, Green Fluorescent Proteins, Long-Term Potentiation, Biophysics, Excitatory Postsynaptic Potentials, Kinesins, In Vitro Techniques, CREB-Binding Protein, Hippocampus, Electric Stimulation, DNA-Binding Proteins, Animals, Immunoprecipitation, Biotinylation, Cycloheximide, Maze Learning, Disks Large Homolog 4 Protein, Guanylate Kinases, Cells, Cultured
Male, Analysis of Variance, Green Fluorescent Proteins, Long-Term Potentiation, Biophysics, Excitatory Postsynaptic Potentials, Kinesins, In Vitro Techniques, CREB-Binding Protein, Hippocampus, Electric Stimulation, DNA-Binding Proteins, Animals, Immunoprecipitation, Biotinylation, Cycloheximide, Maze Learning, Disks Large Homolog 4 Protein, Guanylate Kinases, Cells, Cultured
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