Dendritic GluN2A Synthesis Mediates Activity-Induced NMDA Receptor Insertion

• Type of Material: Article
• Authors: Sharon A. Swanger, Emory University; Yuncen A. He, Emory University; Joel D. Richter, University of Massachusetts Medical School; Gary Bassell, Emory University
• Language: English
• Date: 2013-05-15
• Publisher: American Association of Neuroscience Nurses; Lippincott Williams and Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 the authors
• Final Published Version (URL): http://www.jneurosci.org/content/33/20/8898.long
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0885-0395
• Volume: 33
• Issue: 20
• Start Page: 8898
• End Page: 8908
• Grant/Funding Information: This research was also supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience NINDS Core Facilities grant, P30NS055077.; We gratefully acknowledge support from the NIH: F31NS063668, T32GM0860512, and T32NS007480 (S.A.S.), and MH085617 (G.J.B.), the Epilepsy Foundation and Lennox & Lombroso Trust Fund (S.A.S.), and NARSAD (G.J.B.).
• Research Categories: Biology, Molecular; Biology, Neuroscience; Biology, Cell

Abstract

Long-term synaptic plasticity involves changes in the expression and membrane insertion of cell surface proteins. Interestingly, the mRNAs encoding many cell surface proteins are localized to dendrites, but whether dendritic protein synthesis is required for activity-induced surface expression of specific proteins is unknown. Herein, we use microfluidic devices to demonstrate that dendritic protein synthesis is necessary for activity-induced insertion of GluN2A-containing NMDA receptors in rat hippocampal neurons. Furthermore, visualization of activity-induced local translation of GluN2A mRNA and membrane insertion of GluN2A protein in dendrites was directly observed and shown to depend on a 3′ untranslated region cytoplasmic polyadenylation element (CPE) and its associated translation complex. These findings uncover a novel mechanism for CPE-mediated post-transcriptional regulation of GluN2A mRNA to control NMDA receptor surface expression during synaptic plasticity.