RNA binding proteins accumulate at the postsynaptic density with synaptic activity.
RNA binding proteins accumulate at the postsynaptic density with synaptic activity.
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DOI：
10.1523/jneurosci.2463-11.2012
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发表时间：
2012-01-11
期刊：
影响因子：
--
通讯作者：
Jordan BA
中科院分区：
文献类型：
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作者：
Zhang G;Neubert TA;Jordan BA
神经元活动引起突触组成的变化，突触组成在经验依赖的可塑性中起重要作用。我们采用了一种改良版的细胞培养氨基酸稳定同位素标记（SILAC）来鉴定从大鼠原代神经元培养物中分离的突触后密度（psd）组成中的活性依赖性修饰。我们发现突触活性改变了约2%的PSD蛋白质组，其中包括多种RNA结合蛋白（RNABPs）的增加。事实上，在37个鉴定的蛋白中，有12个蛋白的水平随突触活性的变化而变化，其中包括异质核核糖核蛋白（hnRNPs） G、A2/B1、M和d。使用shRNAs敲除hnRNPs M和G会导致树突棘数量的改变，这表明这些蛋白在脊柱密度中起着至关重要的作用。突触活性也导致树突和突触多聚(a) mRNA同时增加。然而，这种增加不受hnRNP蛋白M或g敲低的影响。我们的研究结果表明，hnRNP蛋白调节树突棘密度，并可能在突触-树突mRNA代谢中发挥作用。
Neuronal activity elicits changes in synaptic composition that play an important role in experience-dependent plasticity. We employed a modified version of Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) to identify activity-dependent modifications in the composition of postsynaptic densities (PSDs) isolated from rat primary neuronal cultures. We found that synaptic activity altered ~2% of the PSD proteome, which included an increase in diverse RNA binding proteins (RNABPs). Indeed 12 of the 37 identified proteins whose levels changed with synaptic activity were RNABPs and included the heterogeneous nuclear ribonucleoproteins (hnRNPs) G, A2/B1, M and D. Knockdown of hnRNPs M and G using shRNAs resulted in altered numbers of dendritic spines, suggesting a crucial role for these proteins in spine density. Synaptic activity also resulted in a concomitant increase in dendritic and synaptic poly(A) mRNA. However, this increase was not affected by knockdown of hnRNPs M or G. Our results suggest that hnRNP proteins regulate dendritic spine density and may play a role in synapto-dendritic mRNA metabolism.