The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression
The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression
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DOI：
10.1016/j.cell.2007.05.028
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发表时间：
2007-07-13
期刊：
影响因子：
64.5
通讯作者：
Moore, Melissa J.
中科院分区：
文献类型：
--
作者：
Giorgi, Corinna;Yeo, Gene W.;Moore, Melissa J.
正确的神经元功能和几种形式的突触可塑性高度依赖于mRNA翻译的精确控制，特别是在树突中。我们发现eIF 4AIII是一种通过前mRNA剪接加载到mRNA上的核心外显子连接复合物（EJC）组分，与神经元mRNA颗粒和树突状mRNA相关。eIF 4AIII敲低显著增加突触强度和突触处的GLUR 1 AMPA受体丰度。eIF 4AIII耗竭也增加ARC，ARC是维持长时程增强所需的蛋白质; arc mRNA是树突中最丰富的mRNA之一，是无义介导的衰变（NMD）的天然靶标。许多新的NMD候选者，其中一些具有影响突触活动的潜力，也通过计算确定。提出了两种模型，用于翻译依赖性衰变途径如NMD如何可能有利地用作细胞如神经元中蛋白质合成的关键制动器，所述细胞高度依赖于空间和时间限制的蛋白质表达。
tProper neuronal function and several forms of synaptic plasticity are highly dependent on precise control of mRNA translation, particularly in dendrites. We find that eIF4AIII, a core exon junction complex ( EJC) component loaded onto mRNAs by pre- mRNA splicing, is associated with neuronal mRNA granules and dendritic mRNAs. eIF4AIII knockdown markedly increases both synaptic strength and GLUR1 AMPA receptor abundance at synapses. eIF4AIII depletion also increases ARC, a protein required for maintenance of long- term potentiation; arc mRNA, one of the most abundant in dendrites, is a natural target for nonsense-mediated decay ( NMD). Numerous new NMD candidates, some with potential to affect synaptic activity, were also identified computationally. Two models are presented for how translation- dependent decay pathways such as NMD might advantageously function as critical brakes for protein synthesis in cells such as neurons that are highly dependent on spatially and temporally restricted protein expression.