Expression and synaptic targeting of the neuronal immediate-early gene Arc

神经元即刻早期基因Arc受突触活动的动态调节，与神经元回路中的信息处理密切相关。最近的研究表明，Arc在突触可塑性/动态平衡和长时记忆形成中起作用。然而，Arc在突触中作用的分子机制仍然不清楚。因此，我们研究了1)Arc与突触后蛋白之间的相互作用，2)Arc进入突触的活性依赖的靶向，以及3)Arc表达的活性依赖的调节。作为结果，我们获得了以下发现：1)Arc与内吞机械中的蛋白质相互作用，并调节突触上的谷氨酸受体(Chowdhury等人，Neuron，52，p445-459,2007)。2)突触靶向Arc是由神经元活动动态调节的。蛋白质-蛋白质相互作用可能参与了这一过程(Okuno等人，提交)。3)在Arc启动子中表征了几个对活性依赖的、神经元特异性表达至关重要的调控元件。4)利用荧光共振能量转移(FRET)技术在树突棘中显示了Arc与Arc结合蛋白之间的相互作用。

The neuronal immediate early gene Arc is dynamically regulated by synaptic activity and tightly linked to information processing in neuronal circuits. Recent studies have indicated that Arc plays roles in synaptic plasticity/homeostasis and long-term memory formation. However, molecular mechanisms of Arc functions at the synapse have still remained unclear. We therefore investigated 1) interaction between Arc and postsynaptic protein, 2) activity-dependent targeting of Arc into synapses, and 3) activity-dependent regulation of Arc expression. As results, we have obtained following findings.1) Arc interacted with proteins in the endocytic machinery, and regulated glutamate receptors at the synapse (Chowdhury et al., Neuron, 52, p445-459, 2007).2) Synaptic targeting of Arc was dynamically regulated by neuronal activity. Protein-protein interaction was likely involved in this process (Okuno et al., submitted).3) Several regulatory elements that were critical for activity-dependent, neuron-specific expression, were characterized in the Arc promoter.4) Interaction between Arc and an Arc-binding protein was visualized in dendritic spines using a fluorescence resonance energy transfer (FRET) technique.