The glycine arginine-rich domain of the RNA-binding protein nucleolin regulates its subcellular localization.
Amino Acid Sequence
Animals
Axonal Transport
/ genetics
Cell Line, Tumor
Cell Nucleolus
/ metabolism
Ganglia, Spinal
/ cytology
Gene Expression
HEK293 Cells
HeLa Cells
Humans
Kinesins
/ genetics
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mutation
Neurons
/ cytology
Phosphoproteins
/ chemistry
Primary Cell Culture
Protein Domains
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ chemistry
Sciatic Nerve
/ cytology
Nucleolin
axonal transport
cell size regulation
local translation
protein-membrane interaction
subcellular localization
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
18 10 2021
18 10 2021
Historique:
revised:
29
07
2021
received:
27
10
2020
accepted:
03
08
2021
pubmed:
14
9
2021
medline:
15
12
2021
entrez:
13
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34515347
doi: 10.15252/embj.2020107158
pmc: PMC8521312
doi:
Substances chimiques
Kns2 protein, mouse
0
Phosphoproteins
0
RNA, Messenger
0
RNA-Binding Proteins
0
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e107158Subventions
Organisme : NIH HHS
ID : S10 OD016229
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089633
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS117821
Pays : United States
Organisme : NINDS NIH HHS
ID : K01 NS105879
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103481
Pays : United States
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Références
Elife. 2020 Jun 08;9:
pubmed: 32510328
BMC Mol Biol. 2007 Aug 10;8:66
pubmed: 17692122
Nucleic Acids Res. 2018 Jul 6;46(12):5894-5901
pubmed: 29800261
Cell Rep. 2012 Jun 28;1(6):608-16
pubmed: 22773964
Phys Chem Chem Phys. 2011 Feb 21;13(7):2613-26
pubmed: 21212894
Cell. 2019 Jan 10;176(1-2):56-72.e15
pubmed: 30612743
EMBO J. 2021 Oct 18;40(20):e107158
pubmed: 34515347
Drug Discov Today. 2019 Oct;24(10):1985-2001
pubmed: 31271738
RNA. 2003 Oct;9(10):1198-207
pubmed: 13130134
Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):E5391-400
pubmed: 26374839
J Cell Sci. 1993 Jul;105 ( Pt 3):799-806
pubmed: 8408305
Cell Rep. 2018 Feb 6;22(6):1473-1483
pubmed: 29425503
Mol Cell. 2015 Mar 5;57(5):936-947
pubmed: 25747659
J Cell Biol. 2015 Apr 13;209(1):97-110
pubmed: 25869669
Nat Rev Mol Cell Biol. 2019 Oct;20(10):642-657
pubmed: 31350521
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
J Biol Chem. 2005 Sep 23;280(38):32890-6
pubmed: 16051612
J Biol Chem. 2020 May 8;295(19):6605-6628
pubmed: 32111743
BMB Rep. 2019 Oct;52(10):601-606
pubmed: 30670150
Trends Cell Biol. 2013 Jul;23(7):305-10
pubmed: 23511112
Science. 2020 Aug 14;369(6505):842-846
pubmed: 32792398
Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):11923-11928
pubmed: 30397112
Cell. 2001 Nov 16;107(4):489-99
pubmed: 11719189
Nucleic Acids Res. 2010 Sep;38(17):e169
pubmed: 20660011
Cell Rep. 2016 Aug 9;16(6):1664-1676
pubmed: 27477284
Chem Pharm Bull (Tokyo). 2016;64(10):1431-1437
pubmed: 27725497
Biochimie. 2015 Jun;113:78-85
pubmed: 25866190
Science. 2018 Mar 23;359(6382):1416-1421
pubmed: 29567716
ACS Omega. 2020 Mar 05;5(10):5202-5208
pubmed: 32201808
Circ Res. 2009 Dec 4;105(12):1240-7
pubmed: 19875726
Front Mol Neurosci. 2018 Sep 05;11:311
pubmed: 30233312
Nat Rev Mol Cell Biol. 2009 Oct;10(10):682-96
pubmed: 19773780
J Control Release. 2014 Oct 28;192:103-13
pubmed: 25016968
J Proteomics. 2014 Apr 4;100:37-43
pubmed: 24513533
Adv Protein Chem Struct Biol. 2018;111:133-164
pubmed: 29459030
J Mol Biol. 2018 Nov 2;430(23):4650-4665
pubmed: 29913160
Nat Neurosci. 2017 Aug;20(8):1172-1179
pubmed: 28671695
Neurobiol Dis. 2000 Aug;7(4):416-28
pubmed: 10964612
Curr Biol. 2020 Dec 21;30(24):4882-4895.e6
pubmed: 33065005
Chromosoma. 2003 Apr;111(7):461-9
pubmed: 12707784
J Neurosci. 2015 Jul 22;35(29):10429-39
pubmed: 26203138
Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4218-4227
pubmed: 30765518
Anal Chem. 1999 Jul 15;71(14):2871-82
pubmed: 10424174
Cancer Res. 2016 Dec 15;76(24):7181-7193
pubmed: 27754848
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Cell. 2018 Apr 19;173(3):706-719.e13
pubmed: 29677514
Acc Chem Res. 2018 Jun 19;51(6):1455-1464
pubmed: 29799185
J Am Chem Soc. 2014 Dec 17;136(50):17459-67
pubmed: 25405895
Biol Cell. 2009 Mar;101(3):153-67
pubmed: 18637790
Mol Cell Proteomics. 2011 Dec;10(12):M111.010728
pubmed: 21937731
PLoS One. 2007 Feb 14;2(2):e201
pubmed: 17299584
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
Biochemistry. 2020 Mar 31;59(12):1261-1272
pubmed: 32191439
Nat Commun. 2018 Oct 8;9(1):4125
pubmed: 30297821
BMC Biol. 2019 Apr 29;17(1):36
pubmed: 31035993
Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt B):1414-1428
pubmed: 28007579
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
Cancer Res. 2011 Mar 15;71(6):2140-51
pubmed: 21257709
Mol Cell. 2013 Jun 6;50(5):613-23
pubmed: 23746349
Mol Biol Cell. 1993 Dec;4(12):1239-50
pubmed: 8167407
Methods Mol Biol. 2011;714:335-52
pubmed: 21431751
Phys Chem Chem Phys. 2014 Oct 14;16(38):20785-95
pubmed: 25166723
Nat Commun. 2018 Aug 22;9(1):3358
pubmed: 30135423
J Biochem. 2021 Feb 6;169(1):87-100
pubmed: 32785674
Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):16883-8
pubmed: 21969533
J Comput Chem. 2014 Oct 15;35(27):1997-2004
pubmed: 25130509
Neuron. 2000 Oct;28(1):41-51
pubmed: 11086982
Hum Genet. 2017 Sep;136(9):1193-1214
pubmed: 28762175
Cell. 2019 Sep 19;179(1):147-164.e20
pubmed: 31539493
Sci Adv. 2020 Mar 13;6(11):eaaz1588
pubmed: 32201729