逆转录病毒样 Gag 蛋白 Arc1 结合 RNA 并穿越突触小泡。
Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons.
机构信息
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
出版信息
Cell. 2018 Jan 11;172(1-2):262-274.e11. doi: 10.1016/j.cell.2017.12.022.
Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles. This loading and transfer depends on the darc1-mRNA 3' untranslated region, which contains retrotransposon-like sequences. Disrupting transfer blocks synaptic plasticity, suggesting that transfer of dArc1 complexed with its mRNA is required for this function. Notably, cultured cells also release extracellular vesicles containing the Gag region of the Copia retrotransposon complexed with its own mRNA. Taken together, our results point to a trans-synaptic mRNA transport mechanism involving retrovirus-like capsids and extracellular vesicles.
Arc/Arg3.1 对于突触可塑性和认知至关重要，该基因的突变与自闭症和精神分裂症有关。Arc 具有类似于逆转录病毒/逆转座子 Gag 样蛋白的结构域，该结构域可以组装成一种衣壳，将病毒 RNA 包装起来。这种结构域在可塑性分子中的意义尚不确定。在这里，我们报告说果蝇 Arc1 蛋白形成衣壳样结构，在神经元中结合 darc1 mRNA，并被装载到从运动神经元转移到肌肉的细胞外囊泡中。这种装载和转移依赖于 darc1-mRNA 的 3'非翻译区，该区域包含逆转座子样序列。干扰转移会阻止突触可塑性，这表明与 dArc1 及其 mRNA 结合的复合物的转移对于该功能是必需的。值得注意的是，培养细胞也会释放含有 Copia 逆转座子复合物及其自身 mRNA 的 Gag 区的细胞外囊泡。总之，我们的研究结果表明存在一种涉及逆转录病毒样衣壳和细胞外囊泡的跨突触 mRNA 运输机制。
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