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The glycine arginine-rich domain of the RNA-binding protein nucleolin regulates its subcellular localization

E. Doron-Mandel, I. Koppel, O. Abraham, I. Rishal, TP. Smith, CN. Buchanan, PK. Sahoo, J. Kadlec, JA. Oses-Prieto, R. Kawaguchi, S. Alber, EE. Zahavi, P. Di Matteo, A. Di Pizio, DA. Song, N. Okladnikov, D. Gordon, S. Ben-Dor, R. Haffner-Krausz,...

. 2021 ; 40 (20) : e107158. [pub] 20210913

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22003450

Grantová podpora
S10 OD016229 NIH HHS - United States
R01 NS089633 NINDS NIH HHS - United States
R01 NS117821 NINDS NIH HHS - United States
K01 NS105879 NINDS NIH HHS - United States
P41 GM103481 NIGMS NIH HHS - United States

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.

Citace poskytuje Crossref.org

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$a Koppel, Indrek $u Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel
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