PMID- 26088419
OWN - NLM
STAT- MEDLINE
DCOM- 20160601
LR  - 20210309
IS  - 1748-7838 (Electronic)
IS  - 1001-0602 (Print)
IS  - 1001-0602 (Linking)
VI  - 25
IP  - 7
DP  - 2015 Jul
TI  - Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is 
      dependent on endoplasmic reticulum chaperone Bip and involved in fear memory.
PG  - 818-36
LID - 10.1038/cr.2015.75 [doi]
AB  - The N-methyl-D-aspartate receptor (NMDAR) in adult forebrain is a heterotetramer 
      mainly composed of two GluN1 subunits and two GluN2A and/or GluN2B subunits. The 
      synaptic expression and relative numbers of GluN2A- and GluN2B-containing NMDARs 
      play critical roles in controlling Ca(2+)-dependent signaling and synaptic 
      plasticity. Previous studies have suggested that the synaptic trafficking of 
      NMDAR subtypes is differentially regulated, but the precise molecular mechanism 
      is not yet clear. In this study, we demonstrated that Bip, an endoplasmic 
      reticulum (ER) chaperone, selectively interacted with GluN2A and mediated the 
      neuronal activity-induced assembly and synaptic incorporation of the 
      GluN2A-containing NMDAR from dendritic ER. Furthermore, the GluN2A-specific 
      synaptic trafficking was effectively disrupted by peptides interrupting the 
      interaction between Bip and GluN2A. Interestingly, fear conditioning in mice was 
      disrupted by intraperitoneal injection of the interfering peptide before 
      training. In summary, we have uncovered a novel mechanism for the 
      activity-dependent supply of synaptic GluN2A-containing NMDARs, and demonstrated 
      its relevance to memory formation.
FAU - Zhang, Xiao-min
AU  - Zhang XM
AD  - 1] Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry 
      of Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China [2] Department of 
      Physiology, Kunming Medical University, Kunming, Yunnan 650500, China.
FAU - Yan, Xun-yi
AU  - Yan XY
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Yang, Qian
AU  - Yang Q
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Ye, Mao
AU  - Ye M
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Cao, Wei
AU  - Cao W
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Qiang, Wen-bin
AU  - Qiang WB
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Zhu, Li-jun
AU  - Zhu LJ
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Du, Yong-lan
AU  - Du YL
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Xu, Xing-xing
AU  - Xu XX
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Wang, Jia-sheng
AU  - Wang JS
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Xu, Fei
AU  - Xu F
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Lu, Wei
AU  - Lu W
AD  - Key Laboratory of Developmental Genes and Human Disease (Ministry of Education of 
      China), Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 
      211189, China.
FAU - Qiu, Shuang
AU  - Qiu S
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Yang, Wei
AU  - Yang W
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
FAU - Luo, Jian-hong
AU  - Luo JH
AD  - Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of 
      Health of China), Collaborative Innovation Center for Brain Science, Zhejiang 
      University School of Medicine, Hangzhou, Zhejiang 310058, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150619
PL  - England
TA  - Cell Res
JT  - Cell research
JID - 9425763
RN  - 0 (GRP78 protein, rat)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A)
SB  - IM
MH  - Animals
MH  - Endoplasmic Reticulum/*metabolism
MH  - Fear/*physiology
MH  - Heat-Shock Proteins/*metabolism
MH  - Memory/*physiology
MH  - Neuronal Plasticity/physiology
MH  - Neurons/metabolism
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synapses/*metabolism
PMC - PMC4493282
EDAT- 2015/06/20 06:00
MHDA- 2016/06/02 06:00
PMCR- 2016/07/01
CRDT- 2015/06/20 06:00
PHST- 2014/10/08 00:00 [received]
PHST- 2015/03/02 00:00 [revised]
PHST- 2015/05/04 00:00 [accepted]
PHST- 2015/06/20 06:00 [entrez]
PHST- 2015/06/20 06:00 [pubmed]
PHST- 2016/06/02 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - cr201575 [pii]
AID - 10.1038/cr.2015.75 [doi]
PST - ppublish
SO  - Cell Res. 2015 Jul;25(7):818-36. doi: 10.1038/cr.2015.75. Epub 2015 Jun 19.