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Molecular motor KIF17 is fundamental for memory and learning via differential support of synaptic NR2A/2B levels.
- Source :
-
Neuron [Neuron] 2011 Apr 28; Vol. 70 (2), pp. 310-25. - Publication Year :
- 2011
-
Abstract
- Kinesin superfamily motor protein 17 (KIF17) is a candidate transporter of N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). Disruption of the murine kif17 gene inhibits NR2B transport, accompanied by decreased transcription of nr2b, resulting in a loss of synaptic NR2B. In kif17(-/-) hippocampal neurons, the NR2A level is also decreased because of accelerated ubiquitin-proteasome system-dependent degradation. Accordingly, NMDA receptor-mediated synaptic currents, early and late long-term potentiation, long-term depression, and CREB responses are attenuated in kif17(-/-) neurons, concomitant with a hippocampus-dependent memory impairment in knockout mice. In wild-type neurons, CREB is activated by synaptic inputs, which increase the levels of KIF17 and NR2B. Thus, KIF17 differentially maintains the levels of NR2A and NR2B, and, when synapses are stimulated, the NR2B/KIF17 complex is upregulated on demand through CREB activity. These KIF17-based mechanisms for maintaining NR2A/2B levels could underlie multiple phases of memory processes in vivo.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Analysis of Variance
Animals
Behavior, Animal
Biophysics methods
Biotinylation
CREB-Binding Protein metabolism
Cell Line, Transformed
Cell Movement genetics
Cells, Cultured
Cycloheximide pharmacology
Down-Regulation genetics
Electric Stimulation methods
Enzyme Inhibitors pharmacology
Excitatory Amino Acid Agents pharmacology
Excitatory Postsynaptic Potentials genetics
Excitatory Postsynaptic Potentials physiology
Fear
Green Fluorescent Proteins genetics
Hippocampus metabolism
Humans
Immunoprecipitation methods
In Vitro Techniques
Kinesins deficiency
Mice
Mice, Transgenic
Neurons drug effects
Neurons physiology
Patch-Clamp Techniques
Proteasome Endopeptidase Complex metabolism
Protein Synthesis Inhibitors pharmacology
Protein Transport genetics
RNA, Messenger metabolism
Synaptophysin metabolism
Time Factors
Time-Lapse Imaging methods
Transfection
Ubiquitin metabolism
Kinesins physiology
Maze Learning physiology
Receptors, N-Methyl-D-Aspartate metabolism
Recognition, Psychology physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 21521616
- Full Text :
- https://doi.org/10.1016/j.neuron.2011.02.049