A Heterologous Cell Model for Studying the Role of T-Cell Intracellular Antigen 1 in Welander Distal Myopathy.
TIA1
Welander distal myopathy
autophagy
gene expression
stress granules
Journal
Molecular and cellular biology
ISSN: 1098-5549
Titre abrégé: Mol Cell Biol
Pays: United States
ID NLM: 8109087
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
19
06
2018
accepted:
09
10
2018
pubmed:
24
10
2018
medline:
23
10
2019
entrez:
24
10
2018
Statut:
epublish
Résumé
Welander distal myopathy (WDM) is a muscle dystrophy characterized by adult-onset distal muscle weakness, prevalently impacting the distal long extensors of the hands and feet. WDM is an autosomal dominant disorder caused by a missense mutation (c.1362G>A; p.E384K) in the TIA1 (T-cell intracellular antigen 1) gene, which encodes an RNA-binding protein basically required for the posttranscriptional regulation of RNAs. We have developed a heterologous cell model of WDM to study the molecular and cellular events associated with mutated TIA1 expression. Specifically, we analyzed how this mutation affects three regulatory functions mediated by TIA1: (i) control of alternative SMN2 (survival motor neuron 2) splicing; (ii) formation, assembly, and disassembly of stress granules; and (iii) mitochondrial dynamics and its consequences for mitophagy, autophagy, and apoptosis. Our results show that whereas WDM-associated TIA1 expression had only a mild effect on SMN2 splicing, it led to suboptimal adaptation to environmental stress, with exacerbated stress granule formation that was accompanied by mitochondrial dysfunction and autophagy. Overall, our observations indicate that some aspects of the cell phenotype seen in muscle of patients with WDM can be recapitulated by ectopic expression of WDM-TIA1 in embryonic kidney cells, highlighting the potential of this model to investigate the pathogenesis of this degenerative disease and possible therapeutics.
Identifiants
pubmed: 30348840
pii: MCB.00299-18
doi: 10.1128/MCB.00299-18
pmc: PMC6290374
pii:
doi:
Substances chimiques
RNA-Binding Proteins
0
T-Cell Intracellular Antigen-1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2018 American Society for Microbiology.
Références
Proc Natl Acad Sci U S A. 2018 Mar 13;115(11):2734-2739
pubmed: 29483269
Cell Stress Chaperones. 2002 Apr;7(2):213-21
pubmed: 12380690
Mol Cell Biol. 2008 Feb;28(4):1240-51
pubmed: 18086893
Mol Biol Cell. 2004 Dec;15(12):5383-98
pubmed: 15371533
EMBO J. 2002 Dec 16;21(24):6882-92
pubmed: 12486009
Cell Rep. 2018 May 29;23(9):2550-2558
pubmed: 29847787
EMBO J. 2000 Aug 1;19(15):4154-63
pubmed: 10921895
Nat Commun. 2016 Jan 07;7:10252
pubmed: 26738979
J Neurol Sci. 1975 Oct;26(2):147-57
pubmed: 126303
J Cell Biol. 1999 Dec 27;147(7):1431-42
pubmed: 10613902
Mol Cell. 2009 Dec 25;36(6):932-41
pubmed: 20064460
Mol Cell. 2017 Nov 16;68(4):808-820.e5
pubmed: 29129640
Curr Opin Struct Biol. 2005 Feb;15(1):94-8
pubmed: 15718139
Cell. 1991 Nov 1;67(3):629-39
pubmed: 1934064
Mol Cell. 2000 Nov;6(5):1089-98
pubmed: 11106748
Nucleic Acids Res. 2017 Jun 20;45(11):6761-6774
pubmed: 28379442
Cell Rep. 2018 Feb 6;22(6):1401-1412
pubmed: 29425497
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2331-6
pubmed: 9482885
Neuromuscul Disord. 1998 Apr;8(2):111-4
pubmed: 9608564
Cell Rep. 2017 May 2;19(5):919-927
pubmed: 28467905
Aging (Albany NY). 2009 Jul 26;1(8):681-98
pubmed: 20157551
Cell Rep. 2018 May 1;23(5):1357-1372
pubmed: 29719250
J Clin Invest. 2018 Mar 1;128(3):1164-1177
pubmed: 29457785
Mol Cell Biol. 2006 Apr;26(7):2716-27
pubmed: 16537914
J Immunol. 1994 May 15;152(10):4937-45
pubmed: 8176212
Cell. 2018 Jan 25;172(3):590-604.e13
pubmed: 29373831
Front Neurol. 2018 Mar 19;9:147
pubmed: 29599744
Cell Cycle. 2015;14(13):2033-43
pubmed: 26036275
Mol Cell Biol. 2000 Sep;20(17):6287-99
pubmed: 10938105
PLoS Biol. 2010 Oct 26;8(10):e1000530
pubmed: 21048981
J Clin Invest. 2013 Mar;123(3):951-7
pubmed: 23454757
Mol Cell Biol. 2005 Nov;25(21):9520-31
pubmed: 16227602
Nucleic Acids Res. 1996 Oct 1;24(19):3829-35
pubmed: 8871565
Mol Biol Cell. 2002 Jan;13(1):195-210
pubmed: 11809833
Nat Neurosci. 2018 Jan;21(1):72-80
pubmed: 29273772
J Biol Chem. 2007 Jul 6;282(27):19410-7
pubmed: 17488725
Mol Cell Biol. 2017 Aug 11;37(17):
pubmed: 28630277
Mol Cell. 2018 May 17;70(4):588-601.e6
pubmed: 29754822
J Biol Chem. 2007 Aug 17;282(33):24131-45
pubmed: 17580304
Cell Metab. 2014 May 6;19(5):757-66
pubmed: 24561260
Autophagy. 2007 Sep-Oct;3(5):452-60
pubmed: 17534139
Cell. 2018 Jul 26;174(3):688-699.e16
pubmed: 29961577
Trends Cell Biol. 2018 Jun;28(6):420-435
pubmed: 29602697
Ann Neurol. 1999 Sep;46(3):399-404
pubmed: 10482271
Acta Med Scand Suppl. 1951;265:1-124
pubmed: 14894174
Sci Rep. 2017 Aug 3;7(1):7183
pubmed: 28775379
Cell Rep. 2016 May 17;15(7):1455-1466
pubmed: 27160897
Ann Neurol. 2013 Apr;73(4):500-9
pubmed: 23401021
Hum Mutat. 2013 Apr;34(4):572-7
pubmed: 23348830
Mol Cell. 2015 Nov 19;60(4):685-96
pubmed: 26549682
Mol Cell. 2018 Apr 5;70(1):175-187.e8
pubmed: 29576526
Mol Cell Biol. 2007 Oct;27(19):6806-17
pubmed: 17682065
Methods Mol Biol. 2010;649:479-91
pubmed: 20680853
J Cell Sci. 2002 Aug 15;115(Pt 16):3227-34
pubmed: 12140254
Cell Rep. 2018 Jan 2;22(1):59-71
pubmed: 29298433
Int J Mol Sci. 2014 Dec 16;15(12):23377-88
pubmed: 25522169
Mol Cell Biol. 2007 Sep;27(18):6265-78
pubmed: 17620417
Neuron. 2017 Aug 16;95(4):808-816.e9
pubmed: 28817800
Genome Biol. 2009;10(8):R87
pubmed: 19709424
Cell Death Dis. 2015 Mar 05;6:e1669
pubmed: 25741594
Cell. 2018 May 3;173(4):958-971.e17
pubmed: 29628143
Neuromuscul Disord. 2002 Aug;12(6):544-7
pubmed: 12117477
Mol Cell Biol. 2011 Mar;31(5):935-54
pubmed: 21189287
Mol Cell. 2018 Feb 15;69(4):622-635.e6
pubmed: 29429924
Neuromuscul Disord. 1998 Apr;8(2):115-8
pubmed: 9608565
Cell Death Differ. 2017 Jan;24(1):49-58
pubmed: 27612012
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8681-5
pubmed: 1326761