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Direct interaction between GluR2 and GAPDH regulates AMPAR-mediated excitotoxicity Wang, Min; Li, Shupeng; Zhang, Hongyu; Pei, Lin; Zou, Shengwei; Lee, Frank J S; Wang, Yu T; Liu, Fang

Abstract

Over-activation of AMPARs (α−amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors) is implicated in excitotoxic neuronal death associated with acute brain insults, such as ischemic stroke. However, the specific molecular mechanism by which AMPARs, especially the calcium-impermeable AMPARs, induce neuronal death remains poorly understood. Here we report the identification of a previously unrecognized molecular pathway involving a direct protein-protein interaction that underlies GluR2-containing AMPAR-mediated excitotoxicity. Agonist stimulation of AMPARs promotes GluR2/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) complex formation and subsequent internalization. Disruption of GluR2/GAPDH interaction by administration of an interfering peptide prevents AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia.

Item Metadata

Title
Direct interaction between GluR2 and GAPDH regulates AMPAR-mediated excitotoxicity
Creator
Wang, Min; Li, Shupeng; Zhang, Hongyu; Pei, Lin; Zou, Shengwei; Lee, Frank J S; Wang, Yu T; Liu, Fang
Contributor
University of British Columbia. Djavad Mowafaghian Centre for Brain Health
Publisher
BioMed Central
Date Issued
2012-04-26
Description
Over-activation of AMPARs (α−amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors) is implicated in excitotoxic neuronal death associated with acute brain insults, such as ischemic stroke. However, the specific molecular mechanism by which AMPARs, especially the calcium-impermeable AMPARs, induce neuronal death remains poorly understood. Here we report the identification of a previously unrecognized molecular pathway involving a direct protein-protein interaction that underlies GluR2-containing AMPAR-mediated excitotoxicity. Agonist stimulation of AMPARs promotes GluR2/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) complex formation and subsequent internalization. Disruption of GluR2/GAPDH interaction by administration of an interfering peptide prevents AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia.
Genre
Article
Type
Text
Language
eng
Date Available
2016-01-11
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0223275
URI
http://hdl.handle.net/2429/56402
Affiliation
Non UBC; Medicine, Faculty of
Citation
Molecular Brain. 2012 Apr 26;5(1):13
Publisher DOI
10.1186/1756-6606-5-13
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Wang et al.; licensee BioMed Central Ltd.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)