Steward Oswald, Farris Shannon, Pirbhoy Patricia S, Darnell Jennifer, Driesche Sarah J Van
Reeve-Irvine Research Center, University of California Irvine Irvine, CA, USA ; Department of Anatomy and Neurobiology, University of California Irvine Irvine, CA, USA ; Department of Neurobiology and Behavior, University of California Irvine Irvine, CA, USA ; Center for the Neurobiology of Learning and Memory, University of California Irvine Irvine, CA, USA.
Reeve-Irvine Research Center, University of California Irvine Irvine, CA, USA ; Department of Anatomy and Neurobiology, University of California Irvine Irvine, CA, USA.
Front Mol Neurosci. 2015 Jan 12;7:101. doi: 10.3389/fnmol.2014.00101. eCollection 2014.
Arc is a unique immediate early gene whose expression is induced as synapses are being modified during learning. The uniqueness comes from the fact that newly synthesized Arc mRNA is rapidly transported throughout dendrites where it localizes near synapses that were recently activated. Here, we summarize aspects of Arc mRNA translation in dendrites in vivo, focusing especially on features of its expression that are paradoxical or that donot fit in with current models of how Arc protein operates. Findings from in vivo studies that donot quite fit include: (1) Following induction of LTP in vivo, Arc mRNA and protein localize near active synapses, but are also distributed throughout dendrites. In contrast, Arc mRNA localizes selectively near active synapses when stimulation is continued as Arc mRNA is transported into dendrites; (2) Strong induction of Arc expression as a result of a seizure does not lead to a rundown of synaptic efficacy in vivo as would be predicted by the hypothesis that high levels of Arc cause glutamate receptor endocytosis and LTD. (3) Arc protein is synthesized in the perinuclear cytoplasm rapidly after transcriptional activation, indicating that at least a pool of Arc mRNA is not translationally repressed to allow for dendritic delivery; (4) Increases in Arc mRNA in dendrites are not paralleled by increases in levels of exon junction complex (EJC) proteins. These results of studies of mRNA trafficking in neurons in vivo provide a new perspective on the possible roles of Arc in activity-dependent synaptic modifications.
Arc是一种独特的即早基因，其表达在学习过程中突触被修饰时被诱导。其独特性源于新合成的Arc mRNA会迅速运输到整个树突中，并定位在最近被激活的突触附近。在这里，我们总结了体内树突中Arc mRNA翻译的各个方面，特别关注其表达中自相矛盾或不符合当前Arc蛋白作用模型的特征。体内研究中不太符合的发现包括：（1）在体内诱导长时程增强（LTP）后，Arc mRNA和蛋白定位于活跃突触附近，但也分布在整个树突中。相比之下，当刺激持续且Arc mRNA被运输到树突中时，Arc mRNA会选择性地定位于活跃突触附近；（2）癫痫发作导致Arc表达强烈诱导，但在体内并不会像高水平Arc导致谷氨酸受体内吞和长时程抑制（LTD）这一假设所预测的那样导致突触效能降低。（3）转录激活后，Arc蛋白在核周细胞质中迅速合成，这表明至少有一部分Arc mRNA没有被翻译抑制，以便进行树突运输；（4）树突中Arc mRNA的增加与外显子连接复合体（EJC）蛋白水平的增加并不平行。这些体内神经元mRNA运输的研究结果为Arc在活动依赖性突触修饰中的可能作用提供了新的视角。
