Postnatal Deamidation of 4E-BP2 in Brain Enhances Its Association with Raptor and Alters Kinetics of Excitatory Synaptic Transmission

被引：78

作者：

Bidinosti, Michael ^{[1
,2
]}

Ran, Israeli ^{[3
]}

Sanchez-Carbente, Maria R. ^{[4
]}

Martineau, Yvan ^{[1
,2
]}

Gingras, Anne-Claude ^{[5
,6
]}

Gkogkas, Christos ^{[1
,2
]}

Raught, Brian ^{[7
,8
]}

Bramham, Clive R. ^{[9
,10
]}

Sossin, Wayne S. ^{[11
]}

Costa-Mattioli, Mauro ^{[1
,2
]}

DesGroseillers, Luc ^{[4
]}

Lacaille, Jean-Claude ^{[3
]}

Sonenberg, Nahum ^{[1
,2
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[2] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3G 1Y6, Canada

[3] Univ Montreal, Dept Physiol, Montreal, PQ H3C 3J7, Canada

[4] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

[5] Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[6] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada

[7] Univ Toronto, Ontario Canc Inst, McLaughlin Ctr Mol Med, Toronto, ON M2G 1L7, Canada

[8] Univ Toronto, Dept Med Biophys, Toronto, ON M2G 1L7, Canada

[9] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway

[10] Univ Bergen, Bergen Mental Hlth Res Ctr, N-5009 Bergen, Norway

[11] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada

来源：

MOLECULAR CELL | 2010年 / 37卷 / 06期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

CAP-DEPENDENT TRANSLATION; LONG-TERM POTENTIATION; DENDRITIC PROTEIN-SYNTHESIS; MAMMALIAN TARGET; RAPAMYCIN MTOR; PHAS-I; 4E-BINDING PROTEIN-1; SECONDARY STRUCTURE; SIGNALING PATHWAY; MESSENGER-RNAS;

D O I：

10.1016/j.molcel.2010.02.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The eIF4E-binding proteins (4E-BPs) repress translation initiation by preventing eIF4F complex formation. Of the three mammalian 4E-BPs, only 4E-BP2 is enriched in the mammalian brain and plays an important role in synaptic plasticity and learning and memory formation. Here we describe asparagine deamidation as a brain-specific posttranslational modification of 4E-BP2. Deamidation is the spontaneous conversion of asparagines to aspartates. Two deamidation sites were mapped to an asparagine-rich sequence unique to 4E-BP2. Deamidated 4E-BP2 exhibits increased binding to the mammalian target of rapamycin (mTOR)-binding protein raptor, which effects its reduced association with eIF4E. 4E-BP2 deamidation occurs during postnatal development, concomitant with the attenuation of the activity of the PI3K-Akt-mTOR signaling pathway. Expression of deamidated 4E-BP2 in 4E-BP2(-/-) neurons yielded mEPSCs exhibiting increased charge transfer with slower rise and decay kinetics relative to the wildtype form. 4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signaling.

引用

页码：797 / 808

页数：12

共 78 条

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