Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons
Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons
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DOI：
10.1038/nn1867
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发表时间：
2007-04-01
影响因子：
25
通讯作者：
Ziff, Edward B.
中科院分区：
文献类型：
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作者：
Jordan, Bryen A.;Fernholz, Brian D.;Ziff, Edward B.
神经元的发育、可塑性和存活需要活性依赖的突触-核信号传导。大多数研究暗示在这种现象中基因表达的活性依赖性调节。然而，很少有人知道其他核功能，突触活动的调节。在这里，我们表明，一个新发现的组成部分，大鼠突触后密度（PSD），AIDA-1d，可以调节全球蛋白质合成，通过改变核仁的数量。AIDA-1d通过其C-末端三个氨基酸与支架蛋白PSD-95的前两个突触后密度-95/盘状大/盘状闭塞物-1（PDZ）结构域结合。NMDA受体（NMDARs），也结合到PSD-95的刺激，导致AIDA-1d的Ca 2+非依赖性易位到细胞核，在那里它耦合到Cajal小体，并诱导Cajal小体-核仁协会。长期神经元刺激导致AIDA-1依赖性的核仁数量和蛋白质合成增加。我们认为AIDA-1d通过调节核仁组装介导突触活性和蛋白质生物合成能力控制之间的联系。
Neuronal development, plasticity and survival require activity-dependent synapse-to-nucleus signaling. Most studies implicate an activity-dependent regulation of gene expression in this phenomenon. However, little is known about other nuclear functions that are regulated by synaptic activity. Here we show that a newly identified component of rat postsynaptic densities (PSDs), AIDA-1d, can regulate global protein synthesis by altering nucleolar numbers. AIDA-1d binds to the first two postsynaptic density-95/Discs large/zona occludens-1 (PDZ) domains of the scaffolding protein PSD-95 via its C-terminal three amino acids. Stimulation of NMDA receptors (NMDARs), which are also bound to PSD-95, results in a Ca2+-independent translocation of AIDA-1d to the nucleus, where it couples to Cajal bodies and induces Cajal body-nucleolar association. Long-term neuronal stimulation results in an AIDA-1-dependent increase in nucleolar numbers and protein synthesis. We propose that AIDA-1d mediates a link between synaptic activity and control of protein biosynthetic capacity by regulating nucleolar assembly.