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结合蛋白核仁蛋白的富含甘氨酸精氨酸的结构域调节其亚细胞定位

Nucleolin 是一种多功能 RNA 结合蛋白 (RBP)，具有多种亚细胞定位，包括所有真核细胞中的核仁、肿瘤细胞中的质膜和神经元中的轴突。在这里，我们展示了核仁蛋白的富含甘氨酸精氨酸 (GAR) 的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 序列介导核仁蛋白的质膜相互作用。除了已经报道的 GAR 域参与核仁中的液-液相分离之外，这两种方式都是额外的。核仁蛋白转运到轴突需要 GAR 结构域，杂合 GAR 缺失小鼠显示核仁蛋白货物 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控制生长的 RNA-RBP 复合物的轴突运输，并且是不同亚细胞区室的通用定位决定因素。GAR 域的定位决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有关。