title: Dendritic GluN2A synthesis mediates activity-induced NMDA receptor insertion.
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 used 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 and its associated translation complex. These findings uncover a novel mechanism for cytoplasmic polyadenylation element-mediated posttranscriptional regulation of GluN2A mRNA to control NMDA receptor surface expression during synaptic plasticity.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Swanger
authors.forename: Yuncen A
authors.initials: YA
authors.lastname: He
authors.forename: Joel D
authors.initials: JD
authors.lastname: Richter
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D019921:Biotinylation; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D005998:Glycine / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046210:Microfluidic Analytical Techniques; D016254:Mutagenesis, Insertional / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D026723:Polyadenylation / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000841:Anisomycin; D005998:Glycine; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate