Presenilin-1/γ-secretase controls glutamate release, tyrosine phosphorylation, and surface expression of N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B

Abstract

Background: Presenilin-1/γ-secretase is critical to neuronal function. Results: Inhibition of presenilin-1/γ-secretase increases release of glutamate, stimulatingNMDARand calpain while decreasing phosphorylation and surface expression of neuronal GluN2B. Conclusion: Presenilin-1/γ-secretase regulates glutamate release,NMDAR- dependentcalpain activity, and modification of GluN2B. Significance: This study reveals a role for γ-secretase in release of glutamate, a neurotransmitter central to neuronal function, and excitotoxicity, a stress important to neurodegeneration. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.