Nucleolin is a multifunctional RNA Binding Protein (RBP) with diverse subcellular localizations, including the nucleolus in all eukaryotic cells, the plasma membrane in tumor cells, and the axon in neurons. Here we show that the glycine arginine rich (GAR) domain of nucleolin drives subcellular localization via protein-protein interactions with a kinesin light chain. In addition, GAR sequences mediate plasma membrane interactions of nucleolin. Both these modalities are in addition to the already reported involvement of the GAR domain in liquid-liquid phase separation in the nucleolus. Nucleolin transport to axons requires the GAR domain, and heterozygous GAR deletion mice reveal reduced axonal localization of nucleolin cargo mRNAs and enhanced sensory neuron growth. Thus, the GAR domain governs axonal transport of a growth controlling RNA-RBP complex in neurons, and is a versatile localization determinant for different subcellular compartments. Localization determination by GAR domains may explain why GAR mutants in diverse RBPs are associated with neurodegenerative disease.

中文翻译：

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RNA 结合蛋白核仁素的富含甘氨酸精氨酸的结构域调节其亚细胞定位


核仁蛋白是一种多功能 RNA 结合蛋白 (RBP)，具有多种亚细胞定位，包括所有真核细胞的核仁、肿瘤细胞的质膜和神经元的轴突。在这里，我们证明核仁素的富含甘氨酸精氨酸（GAR）结构域通过与驱动蛋白轻链的蛋白质-蛋白质相互作用来驱动亚细胞定位。此外，GAR 序列介导核仁素的质膜相互作用。这两种模式是除了已经报道的 GAR 结构域参与核仁液-液相分离之外的。核仁素向轴突的运输需要 GAR 结构域，杂合 GAR 缺失小鼠显示核仁素货物 mRNA 的轴突定位减少，感觉神经元生长增强。因此，GAR 结构域控制神经元中生长控制 RNA-RBP 复合物的轴突运输，并且是不同亚细胞区室的多功能定位决定因素。 GAR 结构域的定位确定可以解释为什么不同 RBP 中的 GAR 突变体与神经退行性疾病相关。