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Journal of Neuroscience
Article . 2012 . Peer-reviewed
License: CC BY NC SA
Data sources: Crossref
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Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and MemoryIn Vivo

Authors: Yosuke Takei; Nobutaka Hirokawa; Nobutaka Hirokawa; Xiling Yin; Xue Feng;

Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and MemoryIn Vivo

Abstract

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.

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Keywords

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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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
51
Top 10%
Top 10%
Top 10%
hybrid