Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission.
Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission.
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DOI：
10.1016/j.molcel.2010.02.022
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发表时间：
2010-03-26
期刊：
影响因子：
16
通讯作者：
Sonenberg N
中科院分区：
文献类型：
--
作者：
Bidinosti M;Ran I;Sanchez-Carbente MR;Martineau Y;Gingras AC;Gkogkas C;Raught B;Bramham CR;Sossin WS;Costa-Mattioli M;DesGroseillers L;Lacaille JC;Sonenberg N
eIF 4 E结合蛋白（4 E-BP）通过阻止eIF 4F复合物的形成来抑制翻译起始。在三种哺乳动物4 E-BP中，只有4 E-BP 2在哺乳动物脑中富集，并在突触可塑性和学习记忆形成中起重要作用。在这里，我们描述天冬酰胺脱酰胺作为脑特异性翻译后修饰的4 E-BP 2。脱酰胺作用是天冬酰胺自发转化为谷氨酸盐。两个脱酰胺位点被映射到4 E-BP 2特有的富含天冬酰胺的序列。脱酰胺的4 E-BP 2表现出与哺乳动物雷帕霉素靶标（mTOR）结合蛋白raptor的结合增加，这影响其与eIF 4 E的结合减少。4 E-BP 2脱酰胺作用发生在出生后发育期间，伴随着PI 3 K-Akt-mTOR信号通路活性的减弱。在4 E-BP 2 −/−神经元中表达脱酰胺的4 E-BP 2产生了mEPSC，其表现出增加的电荷转移，相对于野生型形式具有较慢的上升和衰减动力学。4 E-BP 2脱酰胺可能代表PI 3 K-Akt-mTOR信号传导发育减少的补偿机制。
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 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 signalling 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 wild type form. 4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signalling.
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影响因子：
5.3
作者：
Banko, JL;Poulin, F;Klann, E
通讯作者：
Klann, E
影响因子：
4.7
作者：
Gobert, Delphine;Topolnik, Lisa;Lacaille, Jean-Claude
通讯作者：
Lacaille, Jean-Claude
影响因子：
5.3
作者：
Lebeau, Genevieve;Maher-Laporte, Marjolaine;Lacaille, Jean-Claude
通讯作者：
Lacaille, Jean-Claude
影响因子：
64.8
作者：
Colina, Rodney;Costa-Mattioli, Mauro;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
5.3
作者：
Bourdeau, Mathieu L.;Morin, France;Lacaille, Jean-Claude
通讯作者：
Lacaille, Jean-Claude