FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and De Novo GluA2 Translation

被引：31

作者：

Cook, Denise ^{[1
]}

Nuro, Erin ^{[1
]}

Jones, Emma V. ^{[1
]}

Altimimi, Haider F. ^{[1
]}

Farmer, W. Todd ^{[1
]}

Gandin, Valentina ^{[2
,3
]}

Hanna, Edith ^{[1
]}

Zong, Ruiting ^{[4
]}

Barbon, Alessandro ^{[5
,6
]}

Nelson, David L. ^{[4
]}

Topisirovic, Ivan ^{[2
,3
]}

Rochford, Joseph

Stellwagen, David ^{[1
]}

Beique, Jean-Claude ^{[7
,8
]}

Murai, Keith K. ^{[1
]}

机构：

[1] McGill Univ, Ctr Res Neurosci, Dept Neurol & Neurosurg, Res Inst,Hlth Ctr,Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada

[2] McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada

[3] McGill Univ, Dept Oncol, Montreal, PQ H3T 1E2, Canada

[4] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[5] Univ Brescia, Natl Inst Neurosci, Dept Mol & Translat Med, I-25123 Brescia, Italy

[6] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Verdun, PQ H4H 1R3, Canada

[7] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada

[8] Univ Ottawa, Canadian Partnership Stroke Recovery, Ottawa, ON K1H 8M5, Canada

来源：

CELL REPORTS | 2014年 / 9卷 / 04期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

FRAGILE-X-SYNDROME; PROTEIN-SYNTHESIS; AMPA RECEPTORS; MOUSE MODEL; MENTAL-RETARDATION; MESSENGER-RNAS; PLASTICITY; SUBUNIT; TRAFFICKING; EXPRESSION;

D O I：

10.1016/j.celrep.2014.10.028

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1402 / 1416

页数：15

共 43 条

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