FXR1P limits long-term memory, long-lasting synaptic potentiation, and de novo GluA2 translation.

TitleFXR1P limits long-term memory, long-lasting synaptic potentiation, and de novo GluA2 translation.
Publication TypeJournal Article
Year of Publication2014
AuthorsCook D, Nuro E, Jones EV, Altimimi HF, W Farmer T, Gandin V, Hanna E, Zong R, Barbon A, Nelson DL, Topisirovic I, Rochford J, Stellwagen D, Béïque J-C, Murai KK
JournalCell Rep
Volume9
Issue4
Pagination1402-16
Date Published2014 Nov 20
ISSN2211-1247
Keywords5' Untranslated Regions, Animals, Behavior, Animal, Long-Term Potentiation, Memory, Long-Term, Mice, Knockout, Protein Biosynthesis, Receptors, AMPA, RNA, Messenger, RNA-Binding Proteins, Synapses
Abstract

Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP), and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5' UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.

DOI10.1016/j.celrep.2014.10.028
Alternate JournalCell Rep
PubMed ID25456134
PubMed Central IDPMC4254574
Grant List1R21DA026053-01 / DA / NIDA NIH HHS / United States
MOP111152 / / Canadian Institutes of Health Research / Canada
MOP123390 / / Canadian Institutes of Health Research / Canada
R21 DA026053 / DA / NIDA NIH HHS / United States