Karyopherins and condensates.
Amyloid
Chaperone
Condensates
Exportins
FUS,EWS,EWSR1
Fibrils
Importins
Karyopherins
LARKS
LLPS
Liquid-liquid phase separation
Membraneless organnelles
Nuclear Pore Complex
Nuclear export
Nuclear import
Nuclear transport
Protein aggregation
Ran GTPase
Steric zipper
TAF15
TDP-43
Transportin
hnRNP A1
hnRNP A2
Journal
Current opinion in cell biology
ISSN: 1879-0410
Titre abrégé: Curr Opin Cell Biol
Pays: England
ID NLM: 8913428
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
14
01
2020
revised:
26
03
2020
accepted:
04
04
2020
pubmed:
1
6
2020
medline:
8
1
2021
entrez:
1
6
2020
Statut:
ppublish
Résumé
Several aggregation-prone RNA-binding proteins, including FUS, EWS, TAF15, hnRNP A1, hnRNP A2, and TDP-43, are mutated in neurodegenerative diseases. The nuclear-cytoplasmic distribution of these proteins is controlled by proteins in the karyopherin family of nuclear transport factors (Kaps). Recent studies have shown that Kaps not only transport these proteins but also inhibit their self-association/aggregation, acting as molecular chaperones. This chaperone activity is impaired for disease-causing mutants of the RNA-binding proteins. Here, we review physical data on the mechanisms of self-association of several disease-associated RNA-binding proteins, through liquid-liquid phase separation and amyloid fiber formation. In each case, we relate these data to biophysical, biochemical, and cell biological data on the inhibition of self-association by Kaps. Our analyses suggest that Kaps may be effective chaperones because they contain large surfaces with diverse physical properties that enable them to engage multiple different regions of their cargo proteins, blocking self-association.
Identifiants
pubmed: 32474299
pii: S0955-0674(20)30049-1
doi: 10.1016/j.ceb.2020.04.003
pmc: PMC7371519
mid: NIHMS1599048
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Molecular Chaperones
0
beta Karyopherins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
112-123Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM056322
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM069909
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM131963
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuh Min Chook, Consultancy, Third Rock Ventures, MA, USA. Michael K. Rosen, Consultancy, Third Rock Ventures, MA, USA.
Références
J Cell Sci. 2008 Nov 15;121(Pt 22):3778-85
pubmed: 18957508
Cell. 2006 Aug 11;126(3):543-58
pubmed: 16901787
Biochim Biophys Acta. 2011 Sep;1813(9):1578-92
pubmed: 21029753
J Mol Biol. 2018 Mar 16;430(6):822-841
pubmed: 29408485
Cell. 2018 Apr 19;173(3):677-692.e20
pubmed: 29677512
Structure. 2016 Sep 6;24(9):1537-49
pubmed: 27545621
Biochem J. 2015 Jun 15;468(3):353-62
pubmed: 26173234
Cell. 2015 Aug 27;162(5):1066-77
pubmed: 26317470
Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):20881-90
pubmed: 22065782
Biochim Biophys Acta. 2011 Sep;1813(9):1593-606
pubmed: 21029754
J Neurosci. 2010 Jan 13;30(2):639-49
pubmed: 20071528
Neuropathol Appl Neurobiol. 2013 Aug;39(5):553-61
pubmed: 22934812
Brain Res. 2012 Jun 26;1462:61-80
pubmed: 22445064
Trends Neurosci. 2011 Jul;34(7):339-48
pubmed: 21700347
Mol Cell. 2015 Oct 15;60(2):231-41
pubmed: 26455390
Cell. 2003 Feb 21;112(4):441-51
pubmed: 12600309
FEBS Lett. 2014 May 21;588(10):1857-68
pubmed: 24780099
J Cell Biol. 2013 Apr 29;201(3):361-72
pubmed: 23629963
Nat Commun. 2019 May 1;10(1):2006
pubmed: 31043593
Science. 2018 Feb 9;359(6376):698-701
pubmed: 29439243
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12017-21
pubmed: 22778397
Calcif Tissue Int. 2017 Aug;101(2):159-169
pubmed: 28389692
Science. 2009 Feb 27;323(5918):1208-1211
pubmed: 19251628
Sci Rep. 2018 May 4;8(1):7084
pubmed: 29728564
Nat Struct Mol Biol. 2019 Jul;26(7):637-648
pubmed: 31270472
Hum Genet. 2016 Aug;135(8):851-67
pubmed: 27215579
Acta Neuropathol. 2009 Nov;118(5):617-27
pubmed: 19830439
Cell. 1996 Sep 20;86(6):985-94
pubmed: 8808633
Cell. 2015 Nov 5;163(4):829-39
pubmed: 26544936
Elife. 2019 Mar 11;8:
pubmed: 30855230
Science. 2018 May 25;360(6391):918-921
pubmed: 29650702
Nat Struct Mol Biol. 2018 Jun;25(6):463-471
pubmed: 29786080
Elife. 2017 Oct 16;6:
pubmed: 29035199
J Biol Chem. 2004 Oct 22;279(43):44834-40
pubmed: 15299008
Nature. 2007 May 24;447(7143):453-7
pubmed: 17468747
Cell Rep. 2013 Nov 27;5(4):918-25
pubmed: 24268778
Cell. 2015 Oct 22;163(3):734-45
pubmed: 26456112
Nature. 2005 Jun 9;435(7043):773-8
pubmed: 15944695
J Cell Biol. 2019 Jun 3;218(6):1839-1852
pubmed: 31023722
PLoS Biol. 2011 Apr;9(4):e1001052
pubmed: 21541368
Curr Opin Struct Biol. 2010 Dec;20(6):782-90
pubmed: 20951026
J Biol Chem. 2012 Jun 29;287(27):23079-94
pubmed: 22563080
Hum Mol Genet. 2013 Mar 15;22(6):1193-205
pubmed: 23257289
EMBO J. 2012 Nov 14;31(22):4258-75
pubmed: 22968170
Science. 2020 Feb 7;367(6478):694-699
pubmed: 32029630
Cell Rep. 2015 Oct 27;13(4):690-702
pubmed: 26489467
Biochem J. 2017 Apr 7;474(8):1417-1438
pubmed: 28389532
J Am Chem Soc. 2013 Dec 4;135(48):18016-9
pubmed: 24251952
Cell. 1982 Sep;30(2):449-58
pubmed: 6814762
Nucleic Acids Res. 2017 Jul 27;45(13):7984-7996
pubmed: 28575444
FEBS Lett. 2017 Jun;591(11):1489-1507
pubmed: 28380257
Arch Biochem Biophys. 2014 Mar 1;545:53-62
pubmed: 24440310
Expert Opin Biol Ther. 2008 Jul;8(7):969-78
pubmed: 18549326
Science. 2009 Feb 27;323(5918):1205-8
pubmed: 19251627
Cell. 2018 Apr 19;173(3):693-705.e22
pubmed: 29677513
EMBO J. 2011 Jan 19;30(2):427-38
pubmed: 21139563
Curr Opin Struct Biol. 2001 Dec;11(6):703-15
pubmed: 11751052
Nat Struct Mol Biol. 2019 Jul;26(7):619-627
pubmed: 31235914
Cell. 2015 Sep 24;163(1):123-33
pubmed: 26406374
Acta Neuropathol. 2012 Nov;124(5):705-16
pubmed: 22842875
J Biol Chem. 2013 Jul 5;288(27):19614-24
pubmed: 23689371
Annu Rev Cell Dev Biol. 1999;15:607-60
pubmed: 10611974
Acta Neuropathol. 2011 Nov;122(5):591-600
pubmed: 21847626
Cell. 2018 Apr 19;173(3):720-734.e15
pubmed: 29677515
Proc Natl Acad Sci U S A. 2016 May 10;113(19):5263-8
pubmed: 27114554
Cell. 2012 May 11;149(4):753-67
pubmed: 22579281
Sci Rep. 2018 May 4;8(1):7083
pubmed: 29728608
Proc Natl Acad Sci U S A. 1997 May 13;94(10):5055-60
pubmed: 9144189
Elife. 2015 Sep 15;4:
pubmed: 26371551
Cell. 2018 Jul 26;174(3):688-699.e16
pubmed: 29961577
EMBO J. 2002 Feb 1;21(3):377-86
pubmed: 11823430
Cell. 2018 Apr 19;173(3):706-719.e13
pubmed: 29677514
Neurobiol Aging. 2011 Dec;32(12):2323.e27-40
pubmed: 20674093
Mol Cell. 2018 Feb 1;69(3):465-479.e7
pubmed: 29358076
EMBO J. 2010 Aug 18;29(16):2841-57
pubmed: 20606625
Brain. 2011 Sep;134(Pt 9):2595-609
pubmed: 21856723
PLoS Biol. 2008 Jun 3;6(6):e137
pubmed: 18532879
Biochem Biophys Res Commun. 2011 Jan 28;404(4):991-6
pubmed: 21187067
Cell. 2017 Oct 19;171(3):615-627.e16
pubmed: 28942918
Semin Cancer Biol. 2014 Aug;27:52-61
pubmed: 24631835
PLoS Biol. 2011 Apr;9(4):e1000614
pubmed: 21541367
Acta Neuropathol. 2010 Jan;119(1):1-4
pubmed: 19924424
Nature. 2013 Mar 28;495(7442):467-73
pubmed: 23455423
Nat Struct Mol Biol. 2013 Dec;20(12):1443-9
pubmed: 24240615
Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9782-E9791
pubmed: 30279180
Nature. 2009 Apr 30;458(7242):1136-41
pubmed: 19339969
J Mol Biol. 2005 May 6;348(3):575-88
pubmed: 15826655
Mol Cell. 2013 Jun 6;50(5):613-23
pubmed: 23746349
Annu Rev Biochem. 2007;76:647-71
pubmed: 17506639
Nature. 1984 Sep 6-11;311(5981):33-8
pubmed: 6088992
EMBO J. 2018 Mar 1;37(5):
pubmed: 29438978
J Biol Chem. 2017 Nov 17;292(46):19110-19120
pubmed: 28924037
Nat Commun. 2016 Jun 16;7:11952
pubmed: 27306458
J Biol Chem. 2008 May 9;283(19):13302-9
pubmed: 18305110
Acta Neuropathol. 2009 Nov;118(5):605-16
pubmed: 19669651
Exp Cell Res. 2002 Oct 1;279(2):310-20
pubmed: 12243756
Nucleic Acids Res. 2011 Apr;39(7):2781-98
pubmed: 21109527
Neuron. 2015 Nov 18;88(4):678-90
pubmed: 26526393
Rare Dis. 2013 May 29;1:e25200
pubmed: 25002999
Nat Struct Mol Biol. 2018 Apr;25(4):341-346
pubmed: 29610493
PLoS One. 2012;7(10):e47056
pubmed: 23056579
Hum Mol Genet. 2012 Jul 1;21(13):2899-911
pubmed: 22454397