The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis

The Journal of Cell Biology
J Sebastian Gomez-Cavazos, Martin W Hetzer

Abstract

Previously, we identified the nucleoporin gp210/Nup210 as a critical regulator of muscle and neuronal differentiation, but how this nucleoporin exerts its function and whether it modulates nuclear pore complex (NPC) activity remain unknown. Here, we show that gp210/Nup210 mediates muscle cell differentiation in vitro via its conserved N-terminal domain that extends into the perinuclear space. Removal of the C-terminal domain, which partially mislocalizes gp210/Nup210 away from NPCs, efficiently rescues the differentiation defect caused by the knockdown of endogenous gp210/Nup210. Unexpectedly, a gp210/Nup210 mutant lacking the NPC-targeting transmembrane and C-terminal domains is sufficient for C2C12 myoblast differentiation. We demonstrate that the endoplasmic reticulum (ER) stress-specific caspase cascade is exacerbated during Nup210 depletion and that blocking ER stress-mediated apoptosis rescues differentiation of Nup210-deficient cells. Our results suggest that the role of gp210/Nup210 in cell differentiation is mediated by its large luminal domain, which can act independently of NPC association and appears to play a pivotal role in the maintenance of nuclear envelope/ER homeostasis.

References

Jun 1, 1989·The Journal of Cell Biology·R W WozniakG Blobel
Dec 1, 1982·The Journal of Cell Biology·L GeraceC Kondor-Koch
May 5, 2001·International Review of Cytology·B HuppertzP Kaufmann
Jun 2, 2001·The Journal of Biological Chemistry·N P AllenM Rexach
Apr 16, 2002·Molecular Biology of the Cell·Eric R GriffisMaureen A Powers
Aug 28, 2002·The Journal of Cell Biology·Janet M CronshawMichael J Matunis
Aug 29, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qing XieBoris Yoffe
Aug 12, 2004·FEBS Letters·Charlotta ErikssonEinar Hallberg
Oct 27, 2004·Nature Cell Biology·Gwénaël RabutJan Ellenberg
May 18, 2005·The Journal of Cell Biology·Keiko NakanishiNobuhiro Morishima
May 17, 2006·The Journal of Cell Biology·Fabrizia StavruDirk Görlich
Feb 24, 2007·Current Opinion in Genetics & Development·Christopher R Brown, Pamela A Silver
Jun 6, 2007·Nature Reviews. Genetics·Asifa Akhtar, Susan M Gasser
May 7, 2009·Journal of Lipid Research·Joana D AmaralCecília M P Rodrigues
Oct 30, 2010·Current Opinion in Cell Biology·Yun Liang, Martin W Hetzer
Apr 19, 2011·Annual Review of Biochemistry·André HoelzGünter Blobel
Sep 16, 2011·Exercise and Sport Sciences Reviews·Louise DeldicqueMarc Francaux
Jan 24, 2012·Developmental Cell·Maximiliano A D'AngeloMartin W Hetzer
Feb 9, 2012·Seminars in Cancer Biology·Jose I de Las HerasEric C Schirmer
Sep 22, 2012·Current Opinion in Cell Biology·J Sebastian Gomez-Cavazos, Martin W Hetzer
Oct 24, 2012·Nature Reviews. Molecular Cell Biology·Marcela Raices, Maximiliano A D'Angelo
Oct 17, 2013·Apoptosis : an International Journal on Programmed Cell Death·Christian SchöneichVictor Sharov
Jan 7, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gerald Weissmann
Feb 14, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Keiko NakanishiNobuhiro Morishima

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Citations

Mar 12, 2016·Cell·Kevin E Knockenhauer, Thomas U Schwartz
Nov 1, 2016·Nature Structural & Molecular Biology·Xudong ChenDing Xue
Nov 6, 2018·Canadian Journal of Physiology and Pharmacology·Claudia C PrestonRandolph S Faustino
May 12, 2020·Yonsei Medical Journal·Qiao GuXiaoyuan Ni
Jun 18, 2020·Cancers·Marcus WurlitzerThorsten Rieckmann
Oct 17, 2018·Frontiers in Immunology·Annemarie van NieuwenhuijzeAdrian Liston
Apr 21, 2020·Frontiers in Physiology·Asmat Ullah KhanJingxing Dai
Jan 24, 2018·Journal of Cell Science·Alicia A CutlerGrace K Pavlath
Aug 7, 2017·Biomedit︠s︡inskai︠a︡ khimii︠a︡·S E NovikovaA I Archakov
Dec 17, 2020·Development·Valeria GuglielmiMaximiliano A D'Angelo
Nov 27, 2020·Cancer Research·Seong Hwi HongJueng Soo You
Feb 7, 2017·Structure·Paula UplaJavier Fernandez-Martinez

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Methods Mentioned

BETA
confocal microscopy
glycosylation
scraping
profiler
Flow Cytometry
PCR

Software Mentioned

PRALINE
Photoshop
AxioVision Viewer
Excel
Adobe
ImageJ
Prism
ZEN
Imaris

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