Smaug1 mRNA-silencing foci respond to NMDA and modulate synapse formation.
Smaug1 mRNA-silencing foci respond to NMDA and modulate synapse formation.
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DOI：
10.1083/jcb.201108159
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发表时间：
2011-12-26
期刊：
影响因子：
--
通讯作者：
Boccaccio GL
中科院分区：
文献类型：
--
作者：
Baez MV;Luchelli L;Maschi D;Habif M;Pascual M;Thomas MG;Boccaccio GL
S灶是第一个报道的神经元特异性基因沉默灶，它可能控制NMDAR刺激和突触可塑性反应中局部基因的转录。哺乳动物Smaug1/Samd4A是一种翻译抑制因子。在这里，我们发现Smaug1在海马神经元的突触后形成了mRNA沉默的焦点。这些结构被我们命名为S焦点，不同于P小体、应激颗粒或其他迄今所描述的神经元核糖核酸颗粒，是首次描述的神经元特有的基因沉默焦点。聚集不需要与RNA的结合，这表明S焦点的形成不是mRNA沉默的结果。N-甲基-d-天冬氨酸受体的刺激引起S焦点的快速和可逆的分解，瞬时释放转录本(包括CaMKIIαmRNA)以允许它们的翻译。同时，NMDA触发了全球翻译沉默，这表明Smaug1抑制的转录本被特异性激活。Smaug1在突触发生过程中表达，Smaug1基因敲除影响了突触的数量和大小，也引起了对重复去极化刺激的受损反应，如Arc/Arg3.1的诱导减少。我们的结果表明，S灶控制局部翻译，特异性地对NMDA受体的刺激做出反应，并影响突触的可塑性。
S-foci, the first reported mRNA-silencing foci specific to neurons, may control local mRNA translation in response to NMDA receptor stimulation and synaptic plasticity. Mammalian Smaug1/Samd4A is a translational repressor. Here we show that Smaug1 forms mRNA-silencing foci located at postsynapses of hippocampal neurons. These structures, which we have named S-foci, are distinct from P-bodies, stress granules, or other neuronal RNA granules hitherto described, and are the first described mRNA-silencing foci specific to neurons. RNA binding was not required for aggregation, which indicates that S-foci formation is not a consequence of mRNA silencing. N-methyl-d-aspartic acid (NMDA) receptor stimulation provoked a rapid and reversible disassembly of S-foci, transiently releasing transcripts (the CaMKIIα mRNA among others) to allow their translation. Simultaneously, NMDA triggered global translational silencing, which suggests the specific activation of Smaug1-repressed transcripts. Smaug1 is expressed during synaptogenesis, and Smaug1 knockdown affected the number and size of synapses, and also provoked an impaired response to repetitive depolarizing stimuli, as indicated by a reduced induction of Arc/Arg3.1. Our results suggest that S-foci control local translation, specifically responding to NMDA receptor stimulation and affecting synaptic plasticity.
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