| DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke. | |
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MedLine Citation:
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PMID: 20141836 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extrasynaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292-1304 (NR2B(CT)). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2B(CT) that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca(2+) influx through NMDA receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extrasynaptic sites and this interaction acts as a central mediator for stroke damage. |
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Authors:
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Weihong Tu; Xin Xu; Lisheng Peng; Xiaofen Zhong; Wenfeng Zhang; Mangala M Soundarapandian; Cherine Balel; Manqi Wang; Nali Jia; Wen Zhang; Frank Lew; Sic Lung Chan; Yanfang Chen; Youming Lu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cell Volume: 140 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-09 Completed Date: 2010-02-25 Revised Date: 2011-04-21 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 222-34 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neurology and Neuroscience Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA 70112, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Regulatory Proteins / antagonists & inhibitors, genetics, metabolism* Brain / metabolism, pathology Brain Ischemia / drug therapy, metabolism* Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors, genetics, metabolism* Cell Death Mice Neurons / cytology, metabolism Peptides / metabolism Receptors, N-Methyl-D-Aspartate / metabolism* Recombinant Proteins / genetics, metabolism Stroke / drug therapy, metabolism*, pathology tat Gene Products, Human Immunodeficiency Virus / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 AG033282-01A1/AG/NIA NIH HHS; R01 AG033282-02/AG/NIA NIH HHS; R01 AG033282-03/AG/NIA NIH HHS; R01 NS051383-01A2/NS/NINDS NIH HHS; R01 NS051383-02/NS/NINDS NIH HHS; R01 NS051383-03/NS/NINDS NIH HHS; R01 NS051383-04/NS/NINDS NIH HHS; R01 NS051383-05/NS/NINDS NIH HHS; R01 NS051383-06/NS/NINDS NIH HHS; R01AG033282YL/AG/NIA NIH HHS; R01NS5051383YL/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/NMDA receptor 2B; 0/Peptides; 0/Receptors, N-Methyl-D-Aspartate; 0/Recombinant Proteins; 0/tat Gene Products, Human Immunodeficiency Virus; EC 2.7.11.1/death-associated protein kinase; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases |
| Comments/Corrections | |
Comment In:
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Cell. 2010 Jan 22;140(2):174-6
[PMID:
20141829
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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