Upregulation of eIF4E, but not other translation initiation factors, in dendritic spines during memory formation.
Upregulation of eIF4E, but not other translation initiation factors, in dendritic spines during memory formation.
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DOI：
10.1002/cne.25158
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发表时间：
2021-08-01
期刊：
影响因子：
--
通讯作者：
Ostroff L
中科院分区：
文献类型：
--
作者：
Gindina S;Botsford B;Cowansage K;LeDoux J;Klann E;Hoeffer C;Ostroff L
局部翻译可以在远端树突中提供快速的、空间靶向的新蛋白质供应，以支持作为学习基础的突触变化。学习和记忆对翻译控制机制的操纵特别敏感，特别是那些靶向起始步骤的机制，突触处的翻译起始可能是在可塑性期间维持突触特异性的一种手段。起始主要通过真核起始因子（eIF）的复合物将核糖体募集到5' mRNA帽来发生，并且eIF 4 E和eIF 4G 1之间的相互作用是翻译控制途径的特别重要的靶标。eIF 4 E-eIF 4G 1结合的药理学抑制损害了厌恶性巴甫洛夫条件反射的记忆形成以及伴随的外侧杏仁核（LA）树突棘头部中多聚核糖体的增加。这与突触在记忆形成中的起始作用一致，但eIF是否存在于突触附近尚不清楚。为了确定树突棘是否含有eIF和eIF分布是否受到学习的影响，我们结合免疫标记与连续切片透射电子显微镜（ssTEM）体积重建后巴甫洛夫条件下的LA树突。eIF 4 E、eIF 4G 1和eIF 2 α（另一个关键的调控目标）的标记发生在大约一半的树突棘中，但学习效应只发生在eIF 4 E上，它在树突棘的头部上调。我们的研究结果支持的可能性，调节翻译起始作为一种手段，突触特异性蛋白质靶向在学习过程中，并与模型的eIF 4 E可用性作为一个中心点的控制。记忆的形成需要启动新的蛋白质合成以及树突中的蛋白质合成，但尚不清楚启动是否可以发生在树突棘内。我们结合免疫标记和连续切片三维电子显微镜检查三个起始因子，eIF 4 E，eIF 4G 1和eIF 2 α在巴甫洛夫条件记忆形成过程中的杏仁外侧核树突棘的分布。顶行：电子显微照片显示标记的棘（箭头）与突触（箭头）。左下：从连续切片重建的树突片段，红色显示突触。右下角：训练后含有eIF 4 E标记的棘百分比较高，但eIF 4G 1或eIF 2 α标记没有差异。
Local translation can provide a rapid, spatially targeted supply of new proteins in distal dendrites to support synaptic changes that underlie learning. Learning and memory are especially sensitive to manipulations of translational control mechanisms, particularly those that target the initiation step, and translation initiation at synapses could be a means of maintaining synapse specificity during plasticity. Initiation predominantly occurs via recruitment of ribosomes to the 5’ mRNA cap by complexes of eukaryotic initiation factors (eIFs), and the interaction between eIF4E and eIF4G1 is a particularly important target of translational control pathways. Pharmacological inhibition of eIF4E-eIF4G1 binding impairs formation of memory for aversive Pavlovian conditioning as well as the accompanying increase in polyribosomes in the heads of dendritic spines in the lateral amygdala (LA). This is consistent with a role for initiation at synapses in memory formation, but whether eIFs are even present near synapses is unknown. To determine whether dendritic spines contain eIFs and whether eIF distribution is affected by learning, we combined immunolabeling with serial section transmission electron microscopy (ssTEM) volume reconstructions of LA dendrites after Pavlovian conditioning. Labeling for eIF4E, eIF4G1, and eIF2α – another key target of regulation – occurred in roughly half of dendritic spines, but learning effects were only found for eIF4E, which was upregulated in the heads of dendritic spines. Our results support the possibility of regulated translation initiation as a means of synapse-specific protein targeting during learning and are consistent with the model of eIF4E availability as a central point of control. Memory formation requires initiation of new protein synthesis as well as protein synthesis in dendrites, but it is unknown whether initiation can happen within dendritic spines. We combined immunolabeling with serial section 3D electron microscopy to examine the distribution of three initiation factors, eIF4E, eIF4G1, and eIF2α in dendritic spines of the lateral amygdala during formation of a Pavlovian conditioning memory. Top row: Electron micrographs showing labeled spines (arrows) with synapses (arrowheads). Bottom left: Segment of dendrite reconstructed from serial sections with synapses shown in red. Bottom right: The percentage of spines containing labeling for eIF4E was higher after training, but there were no differences for eIF4G1 or eIF2α labeling.
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影响因子：
19
作者：
Buxbaum AR;Yoon YJ;Singer RH;Park HY
通讯作者：
Park HY
影响因子：
2.5
作者：
Dynes, Joseph L.;Steward, Oswald
通讯作者：
Steward, Oswald
DOI：
10.1016/j.mcn.2018.04.004
发表时间：
2018-09
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Bourke AM;Bowen AB;Kennedy MJ
通讯作者：
Kennedy MJ
影响因子：
16.6
作者：
de la Parra C;Ernlund A;Alard A;Ruggles K;Ueberheide B;Schneider RJ
通讯作者：
Schneider RJ
影响因子：
16
作者：
Gruener, Stefan;Peter, Daniel;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa