title: Molecular motor KIF17 is fundamental for memory and learning via differential support of synaptic NR2A/2B levels.
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.
authors.affiliation: Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Xiling
authors.initials: X
authors.lastname: Yin
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Takei
authors.forename: Mizuho A
authors.initials: MA
authors.lastname: Kido
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hirokawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001703:Biophysics / Q000379:methods; D019921:Biotinylation; D050882:CREB-Binding Protein / Q000378:metabolism; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation / Q000235:genetics; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005239:Fear; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D016547:Kinesins / Q000172:deficiency / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D059008:Time-Lapse Imaging / Q000379:methods; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; C409642:KIF17 protein, mouse; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D003513:Cycloheximide; D050882:CREB-Binding Protein; D046988:Proteasome Endopeptidase Complex; D016547:Kinesins