The glycine arginine-rich domain of the RNA-binding protein nucleolin regulates its subcellular localization.
The glycine arginine-rich domain of the RNA-binding protein nucleolin regulates its subcellular localization.
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RNA结合蛋白核仁素的富含甘氨酸的结构域调节其亚细胞定位。
DOI：
10.15252/embj.2020107158
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发表时间：
2021-10-18
期刊：
影响因子：
--
通讯作者：
Fainzilber M
中科院分区：
文献类型：
--
作者：
Doron-Mandel E;Koppel I;Abraham O;Rishal I;Smith TP;Buchanan CN;Sahoo PK;Kadlec J;Oses-Prieto JA;Kawaguchi R;Alber S;Zahavi EE;Di Matteo P;Di Pizio A;Song DA;Okladnikov N;Gordon D;Ben-Dor S;Haffner-Krausz R;Coppola G;Burlingame AL;Jungwirth P;Twiss JL;Fainzilber M
核仁素是一种多功能的RNA结合蛋白（RBP），具有不同的亚细胞定位，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，我们表明核仁素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。这两种方式都是除了已经报道的GAR结构域参与核仁中的液-液相分离之外的。核仁素转运到轴突需要GAR结构域，杂合GAR缺失小鼠显示核仁素货物mRNA的轴突定位减少和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通用定位决定因素。通过GAR结构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相关。核仁素富含甘氨酸精氨酸（GAR）结构域通过直接结合驱动蛋白马达控制轴突的亚细胞定位。
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. The glycine arginine rich (GAR) domain of nucleolin controls subcellular localization in axons by directly binding the kinesin motor.
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影响因子：
5.3
作者：
Kapeli K;Martinez FJ;Yeo GW
通讯作者：
Yeo GW
影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
25
作者：
Chan KY;Jang MJ;Yoo BB;Greenbaum A;Ravi N;Wu WL;Sánchez-Guardado L;Lois C;Mazmanian SK;Deverman BE;Gradinaru V
通讯作者：
Gradinaru V
影响因子：
7.4
作者：
Clauser, KR;Baker, P;Burlingame, AL
通讯作者：
Burlingame, AL
影响因子：
11.2
作者：
Gilles, Maud-Emmanuelle;Maione, Federica;Cascone, Ilaria
通讯作者：
Cascone, Ilaria