Quantitative proteomics identifies proteins that resist translational repression and become dysregulated in ALS-FUS.
Amyotrophic Lateral Sclerosis
/ genetics
Animals
Arsenites
/ pharmacology
Cell Line, Tumor
Coat Protein Complex I
/ metabolism
Cytoplasmic Granules
/ drug effects
Endoplasmic Reticulum
/ drug effects
Golgi Apparatus
/ drug effects
Humans
Mice
Motor Neurons
/ drug effects
Mutation
Protein Biosynthesis
/ drug effects
Proteomics
RNA-Binding Protein FUS
/ genetics
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
17
09
2018
revised:
01
02
2019
accepted:
07
02
2019
pubmed:
27
2
2019
medline:
31
3
2020
entrez:
27
2
2019
Statut:
ppublish
Résumé
Aberrant translational repression is a feature of multiple neurodegenerative diseases. The association between disease-linked proteins and stress granules further implicates impaired stress responses in neurodegeneration. However, our knowledge of the proteins that evade translational repression is incomplete. It is also unclear whether disease-linked proteins influence the proteome under conditions of translational repression. To address these questions, a quantitative proteomics approach was used to identify proteins that evade stress-induced translational repression in arsenite-treated cells expressing either wild-type or amyotrophic lateral sclerosis (ALS)-linked mutant FUS. This study revealed hundreds of proteins that are actively synthesized during stress-induced translational repression, irrespective of FUS genotype. In addition to proteins involved in RNA- and protein-processing, proteins associated with neurodegenerative diseases such as ALS were also actively synthesized during stress. Protein synthesis under stress was largely unperturbed by mutant FUS, although several proteins were found to be differentially expressed between mutant and control cells. One protein in particular, COPBI, was downregulated in mutant FUS-expressing cells under stress. COPBI is the beta subunit of the coat protein I (COPI), which is involved in Golgi to endoplasmic reticulum (ER) retrograde transport. Further investigation revealed reduced levels of other COPI subunit proteins and defects in COPBI-relatedprocesses in cells expressing mutant FUS. Even in the absence of stress, COPBI localization was altered in primary and human stem cell-derived neurons expressing ALS-linked FUS variants. Our results suggest that Golgi to ER retrograde transport may be important under conditions of stress and is perturbed upon the expression of disease-linked proteins such as FUS.
Identifiants
pubmed: 30806671
pii: 5365305
doi: 10.1093/hmg/ddz048
pmc: PMC6586143
doi:
Substances chimiques
Arsenites
0
Coat Protein Complex I
0
RNA-Binding Protein FUS
0
arsenite
N5509X556J
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
2143-2160Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM045443
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS073873
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Références
J Neurosci. 2014 Jun 11;34(24):8083-97
pubmed: 24920614
Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4769-78
pubmed: 25324524
J Neurosci. 2012 Nov 21;32(47):16560-73
pubmed: 23175812
Hum Mol Genet. 2013 Feb 15;22(4):729-36
pubmed: 23175440
Hum Mol Genet. 2011 Apr 1;20(7):1400-10
pubmed: 21257637
J Biol Chem. 2008 Aug 15;283(33):22774-86
pubmed: 18556652
Brain Res. 2009 Jan 16;1249:202-11
pubmed: 19046946
Neurobiol Dis. 2008 Feb;29(2):221-31
pubmed: 17964175
Cell. 2014 Jan 30;156(3):413-27
pubmed: 24485452
Cell. 2015 Aug 27;162(5):1066-77
pubmed: 26317470
Cell Death Dis. 2013 Oct 31;4:e888
pubmed: 24176846
Nat Med. 2018 Aug;24(8):1136-1142
pubmed: 29942091
PLoS Genet. 2011 Mar;7(3):e1002011
pubmed: 21408206
Mol Cell. 2017 Nov 16;68(4):808-820.e5
pubmed: 29129640
J Proteome Res. 2006 Sep;5(9):2339-47
pubmed: 16944946
Acta Neuropathol. 2017 Jun;133(6):887-906
pubmed: 28243725
Neurobiol Aging. 2014 Dec;35(12):2822-2831
pubmed: 25216585
J Neurol Sci. 2006 Jul 15;246(1-2):21-30
pubmed: 16545397
Science. 2009 Feb 27;323(5918):1208-1211
pubmed: 19251628
RNA. 2013 Apr;19(4):498-509
pubmed: 23389473
Hum Mol Genet. 2011 May 1;20(9):1701-11
pubmed: 21300694
Hum Mol Genet. 2015 Dec 20;24(25):7295-307
pubmed: 26464491
Cell Stem Cell. 2015 Nov 5;17(5):569-84
pubmed: 26321202
Anal Chem. 2002 Oct 15;74(20):5383-92
pubmed: 12403597
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Nat Struct Mol Biol. 2011 Nov 13;18(12):1428-31
pubmed: 22081015
J Biol Chem. 2012 May 4;287(19):15635-47
pubmed: 22427648
J Cell Biol. 1990 Dec;111(6 Pt 1):2295-306
pubmed: 2277061
N Engl J Med. 2017 Jul 13;377(2):162-172
pubmed: 28700839
ASN Neuro. 2014 Jun 01;6(4):
pubmed: 25289647
J Biol Chem. 2019 May 3;294(18):7115-7127
pubmed: 30045872
J Cell Biol. 1998 Jan 12;140(1):1-15
pubmed: 9425149
J Cell Biol. 2013 Dec 9;203(5):737-46
pubmed: 24297750
PLoS Biol. 2011 Apr;9(4):e1001052
pubmed: 21541368
J Biomol Screen. 2014 Jan;19(1):44-56
pubmed: 24019256
Sci Rep. 2017 Oct 25;7(1):14035
pubmed: 29070863
Trends Biochem Sci. 2013 Oct;38(10):494-506
pubmed: 24029419
J Proteome Res. 2012 Jun 1;11(6):3487-97
pubmed: 22537090
Hum Mol Genet. 2013 Oct 15;22(20):4043-52
pubmed: 23727837
Mol Neurodegener. 2013 Aug 31;8:30
pubmed: 24090136
Mol Biol Cell. 2014 Sep 1;25(17):2571-8
pubmed: 25009283
J Cell Sci. 2017 Mar 1;130(5):927-937
pubmed: 28096475
Nat Genet. 2014 Feb;46(2):152-60
pubmed: 24336168
Neuron. 2018 Nov 21;100(4):816-830.e7
pubmed: 30344044
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):E11904-E11913
pubmed: 30455313
Science. 2009 Feb 27;323(5918):1205-8
pubmed: 19251627
Sci Rep. 2017 Dec;7(1):115
pubmed: 28273913
PLoS Genet. 2010 May 20;6(5):e1000956
pubmed: 20502676
Proc Natl Acad Sci U S A. 2018 Dec 4;115(49):E11485-E11494
pubmed: 30442662
Nat Rev Neurol. 2010 Apr;6(4):211-20
pubmed: 20234357
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):12842-12844
pubmed: 30504142
J Cell Sci. 2016 May 1;129(9):1892-901
pubmed: 27026526
PLoS Genet. 2013 Oct;9(10):e1003895
pubmed: 24204307
Cell Rep. 2014 Apr 10;7(1):1-11
pubmed: 24703839
J Neurochem. 2009 Nov;111(4):1051-61
pubmed: 19765185
J Proteome Res. 2014 Dec 5;13(12):5707-14
pubmed: 25271054
Proc Natl Acad Sci U S A. 2017 May 16;114(20):E3935-E3943
pubmed: 28396410
EMBO J. 2016 May 17;35(10):1077-97
pubmed: 26951610
PLoS One. 2010 Oct 11;5(10):e13250
pubmed: 20948999
Neurobiol Aging. 2011 Dec;32(12):2323.e27-40
pubmed: 20674093
Mol Cell. 2017 Mar 16;65(6):1044-1055.e5
pubmed: 28306503
Hum Mutat. 2013 Jun;34(6):812-26
pubmed: 23559573
EMBO J. 2010 Aug 18;29(16):2841-57
pubmed: 20606625
Sci Transl Med. 2013 Oct 9;5(206):206ra138
pubmed: 24107777
Nucleic Acids Res. 2009 Jan;37(1):1-13
pubmed: 19033363
Brain. 2011 Sep;134(Pt 9):2595-609
pubmed: 21856723
Eur J Neurol. 2013 Mar;20(3):540-6
pubmed: 23217123
J Cell Sci. 2009 Oct 15;122(Pt 20):3619-26
pubmed: 19812307
Biochim Biophys Acta. 2005 Jul 10;1744(3):406-14
pubmed: 15979510
Nat Neurosci. 2012 Nov;15(11):1488-97
pubmed: 23023293
PLoS One. 2012;7(11):e49021
pubmed: 23145051
J Cell Biol. 2008 Aug 25;182(4):663-73
pubmed: 18725537
Anal Chem. 2003 Sep 1;75(17):4646-58
pubmed: 14632076
Nature. 2013 Mar 28;495(7442):467-73
pubmed: 23455423
Elife. 2015 Feb 26;4:
pubmed: 25719440
Nat Rev Mol Cell Biol. 2005 Apr;6(4):318-27
pubmed: 15803138
Brain. 2017 Jun 1;140(6):1768-1783
pubmed: 28430857
Front Cell Neurosci. 2015 Oct 23;9:423
pubmed: 26557057
Nat Commun. 2016 Feb 04;7:10465
pubmed: 26842965
Cell Death Dis. 2014 Dec 11;5:e1572
pubmed: 25501833
J Cell Biol. 2016 Dec 19;215(6):769-778
pubmed: 27903609
Hum Mol Genet. 2010 Nov 1;19(21):4160-75
pubmed: 20699327
Neuron. 2017 Aug 16;95(4):808-816.e9
pubmed: 28817800
Trends Cell Biol. 2016 Sep;26(9):668-679
pubmed: 27289443
Hum Mol Genet. 2015 Feb 1;24(3):773-86
pubmed: 25274782
Elife. 2015 Jan 26;4:e03971
pubmed: 25621764
Mol Cell Biol. 2011 Mar;31(5):1098-108
pubmed: 21173160
Neuron. 2015 Nov 18;88(4):678-90
pubmed: 26526393