Calpain-mediated Degradation of Myocyte Enhancer Factor 2D Contributes to Excitotoxicity by Activation of Extrasynaptic N-Methyl-d-aspartate Receptors

• Type of Material: Article
• Authors: Gengze Wei, Emory University; Yue Yin, Fourth Military Medical University; Wenming Li, Emory University; Haruhiko Bito, University of Tokyo; Hua She, Emory University; Zixu Mao, Emory University
• Language: English
• Date: 2012-02-17
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://www.jbc.org/content/287/8/5797
• Title of Journal or Parent Work: Journal of Biological Chemistry
• Volume: 287
• Issue: 8
• Start Page: 5797
• End Page: 5805
• Grant/Funding Information: This work was supported in part by National Institutes of Health Grants AG023695, NS048254, ES015317, and ES016731-002 (to Z. M.).; This work was also supported by the Michael J. Fox Foundation (to Z. M.).
• Keywords: Calpain; Neurobiology; Myocyte Enhancer Factor 2D; Glutamate Receptor Ionotropic (AMPA, NMDA); Excitotoxicity; Neurodegeneration; Signal Transduction
• Research Categories: Biology, Neuroscience; Chemistry, Biochemistry

Abstract

Background: Myocyte enhancer factor 2D (MEF2D) plays important roles in neuronal survival. Results: Activation of extrasynaptic NMDAR causes calpain-mediated cleavage of MEF2D. Conclusion: Extrasynaptic NMDA receptors-induced excitotoxicity is in part mediated by degradation of MEF2D. Significance: Learning how MEF2D is dysregulated by excessive NMDA-activated calpain may provide a therapeutic strategy by inhibiting MEF2D degradation for excitotoxicity-associated diseases.