北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 神经生物学系  > 期刊论文
学科主题: 基础医学
题名:
The DREAM Protein Negatively Regulates the NMDA Receptor through Interaction with the NR1 Subunit
作者: Zhang, Ying1,2; Su, Ping1,2; Liang, Ping1,2; Liu, Tao3,4; Liu, Xu5; Liu, Xin-Ying3,4; Zhang, Bo3,4; Han, Tao1,2; Zhu, Yan-Bing1,2; Yin, Dong-Min1,2; Li, Junfa5; Zhou, Zhuan3,4; Wang, Ke-Wei1,2; Wang, Yun1,2
刊名: JOURNAL OF NEUROSCIENCE
发表日期: 2010-06-02
DOI: 10.1523/JNEUROSCI.1312-10.2010
卷: 30, 期:22, 页:7575-7586
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: D-ASPARTATE RECEPTOR ; TRANSCRIPTIONAL REPRESSOR DREAM ; CALCIUM-SENSOR PROTEINS ; GENE-EXPRESSION ; ALPHA-ACTININ ; SPLICE VARIANTS ; POTASSIUM CHANNELS ; KINASE-II ; CALMODULIN ; BINDING
英文摘要:

Glutamate-induced excitotoxicity has been implicated in the etiology of stroke, epilepsy, and neurodegenerative diseases. NMDA receptors (NMDARs) play a pivotal role in excitotoxic injury; however, clinical trials testing NMDAR antagonists as neuroprotectants have been discouraging. The development of novel neuroprotectant molecules is being vigorously pursued. Here, we report that downstream regulatory element antagonist modulator(DREAM) significantly inhibits surface expression of NMDARs and NMDAR-mediated current. Overexpression of DREAM showed neuroprotection against excitotoxic neuronal injury, whereas knockdown of DREAM enhanced NMDA-induced toxicity. DREAM could directly bind to the C0 domain of the NR1 subunit. Although DREAM contains multiple binding sites for the NR1 subunit, residues 21-40 of the N terminus are the main binding site for the NR1 subunit. Thus, 21-40 residues might relieve the autoinhibition conferred by residues 1-50 and derepress the DREAM core domain by a competitive mechanism. Intriguingly, the cell-permeable TAT-21-40 peptide, constructed according to the critical binding site of DREAM to the NR1 subunit, inhibits NMDAR mediated currents in primary cultured hippocampal neurons and has a neuroprotective effect on in vitro neuronal excitotoxic injury and in vivo ischemic brain damage. Moreover, both pretreatment and posttreatment of TAT-21-40 is effective against excitotoxicity. In summary, this work reveals a novel, negative regulator of NMDARs and provides an attractive candidate for the treatment of excitotoxicity-related disease.

语种: 英语
所属项目编号: 2007CB512100 ; 2006CB500800 ; 200800011028 ; 20060001121 ; 30925015 ; 30900582 ; 30830044 ; 30830043 ; 30728009 ; 30770703 ; 7092061
项目资助者: National Basic Research 973 Program of China ; Specialized Research Fund for Doctoral Program of Higher Education ; National Natural Science Foundation of China ; Beijing Natural Science Foundation
WOS记录号: WOS:000278288200015
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52340
Appears in Collections:基础医学院_神经生物学系_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
The DREAM Protein Negatively Regulates the NMDA Receptor through Interaction with the NR1 Subunit.pdf(3738KB)期刊论文出版稿限制开放 联系获取全文

作者单位: 1.Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
3.Peking Univ, Minist Educ & Hlth, Dept Neurobiol, Key Lab Neurosci, Beijing 100191, Peoples R China
4.Peking Univ, State Key Lab Biomembrane Engn, Beijing 100871, Peoples R China
5.Capital Med Univ, Dept Neurobiol, Beijing 100054, Peoples R China

Recommended Citation:
Zhang, Ying,Su, Ping,Liang, Ping,et al. The DREAM Protein Negatively Regulates the NMDA Receptor through Interaction with the NR1 Subunit[J]. JOURNAL OF NEUROSCIENCE,2010,30(22):7575-7586.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Zhang, Ying]'s Articles
[Su, Ping]'s Articles
[Liang, Ping]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Zhang, Ying]‘s Articles
[Su, Ping]‘s Articles
[Liang, Ping]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace