TY - JOUR
T1 - Molecular Motor KIF17 Is Fundamental for Memory and Learning via Differential Support of Synaptic NR2A/2B Levels
AU - Yin, Xiling
AU - Takei, Yosuke
AU - Kido, Mizuho A.
AU - Hirokawa, Nobutaka
N1 - Funding Information:
We thank M. Hollman (Ruhr University) and S. Okabe (The University of Tokyo) for providing NR1 cDNA, A. Barria (Washington University) and R. Malinow (University of California, San Diego) for providing NR2B/NR2A-EGFP constructs, M. Watanabe (Hokkaido University) for providing anti-NR2D antibody, and T. Hensch (RIKEN) and H. Katagiri (RIKEN) for their help and suggestions about electrophysiology. We also thank Masahiko Kawagishi and Keisuke Yamamoto, and all other members of Hirokawa Laboratory for their help and discussion. This work was supported by a grant-in-aid for specially promoted research to N.H. from the Ministry of Education, Culture, Science, Sports and Technology of Japan.
PY - 2011/4/28
Y1 - 2011/4/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2011.02.049
DO - 10.1016/j.neuron.2011.02.049
M3 - Article
C2 - 21521616
AN - SCOPUS:79955088142
SN - 0896-6273
VL - 70
SP - 310
EP - 325
JO - Neuron
JF - Neuron
IS - 2
ER -