Differential roles of NR2A and NR2B subtypes in NMDA receptor-dependent protein synthesis in dendrites.
Protein synthesis in dendrites is critical for long-term synaptic plasticity. Previous studies have identified an essential role of NMDA receptors in control of activity-dependent dendritic protein synthesis, but the contribution of NR2A- and NR2B-containing NMDA receptors, the two predominant subtypes of NMDA receptors in the forebrain, has not been determined. Using a pharmacological approach, we investigated the role of NR2A and NR2B subtypes in the regulation of NMDA-induced dendritic translation of a GFP reporter mRNA controlled by CaMKII untranslated regions (UTRs). We found that ifenprodil and Ro25-6981, two specific inhibitors of NR2B-containing NMDA receptors, did not affect dendritic GFP synthesis induced by NMDA. In contrast, NVP-AAM077, an antagonist that preferentially blocks the NR2A subtype, completely abolished NMDA-induced GFP synthesis in dendrites. Our results together suggest that NR2A but not NR2B subtypes are indispensable for NMDA receptor-dependent dendritic protein synthesis.
Tran
Dang Hai
DH
Department of Neurobiology and Behavior, Center for Neurobiology of Learning and Memory, University of California, Irvine, CA 92697, USA.
Gong
Ruomu
R
Tang
Shao-Jun
SJ
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000166:cytology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D049452:Green Fluorescent Proteins