Arc: building a bridge from viruses to memory.
Arc: building a bridge from viruses to memory.
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DOI：
10.1042/bj20150487
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发表时间：
2015-07-01
期刊：
影响因子：
--
通讯作者：
Shepherd JD
中科院分区：
文献类型：
--
作者：
Day C;Shepherd JD
ARC(活性调节细胞骨架相关蛋白)是一种神经元特异性的即刻早期基因，是哺乳动物大脑中持久形式的突触可塑性和记忆所必需的。ARC的表达是高度动态的，并受到神经元活动和经验的严格调控。突触上Arc蛋白的局部翻译是突触可塑性的关键，突触可塑性是由Arc依赖的AMPA(α-amino-3-hydroxy-5-methylisoxazole-4-propionic酸类型谷氨酸受体的运输所介导的。到目前为止，对Arc蛋白的结构或生物物理性质的研究还很少。最近的研究，包括Myrum等人的研究。发表在468：1期的《生化杂志》上，现在阐明了Arc的一些有趣的生物物理性质。这些发现表明，Arc在柔性连接区周围含有大的N-末端和C-末端结构域，并且纯化的Arc蛋白能够自我寡聚。有趣的是，这些结构域与大多数逆转录病毒的Gag多肽中发现的病毒衣壳蛋白同源。这些研究提供了对Arc如何调控神经元中多种关键细胞生物学过程的洞察，并揭示了类似于细胞内病毒运输的意想不到的生物学。
Arc (activity-regulated cytoskeleton-associated protein) is a neuron-specific immediate early gene that is required for enduring forms of synaptic plasticity and memory in the mammalian brain. Arc expression is highly dynamic, and tightly regulated by neuronal activity and experience. Local translation of Arc protein at synapses is critical for synaptic plasticity, which is mediated by Arc-dependent trafficking of AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-type glutamate receptors. To date, few structural or biophysical properties of Arc protein have been investigated. Recent studies, including that of Myrum et al. published in the 468:1 issue of the Biochemical Journal, now shed light on some intriguing biophysical properties of Arc. These findings show that Arc contains large N- and C-terminal domains around a flexible linker region and that purified Arc protein is capable of self-oligomerization. Intriguingly, these domains show homology with the viral capsid protein found in the gag polypeptide of most retroviruses. These studies provide insight into how Arc may regulate multiple critical cell biological processes in neurons and reveals unanticipated biology that resembles viral trafficking in cells.