Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation.

ELife
Joseph E ChambersStefan J Marciniak

Abstract

Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) to activate the integrated stress response (ISR). In animals, the ISR is antagonised by selective eIF2α phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in complex with a PPP1R15-type regulatory subunit. An unbiased search for additional conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin. Like PP1, G-actin associated with the functional core of PPP1R15 family members and G-actin depletion, by the marine toxin jasplakinolide, destabilised the endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin complex was responsive to global changes in the polymeric status of actin, as was its eIF2α-directed phosphatase activity, while localised G-actin depletion at sites enriched for PPP1R15 enhanced eIF2α phosphorylation and the downstream ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR.

References

Jan 13, 2000·Biochemical and Biophysical Research Communications·T HasegawaK Isobe
May 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Koji KojimaCharles A Vacanti
May 7, 2003·Cell·Francesc MirallesRichard Treisman
Jan 14, 2004·The Journal of Cell Biology·Weibin ShiXu Cao
Jul 13, 2004·Trends in Cell Biology·Ville O PaavilainenPekka Lappalainen
Sep 15, 2004·Trends in Biochemical Sciences·Martin A Wear, John A Cooper
Dec 3, 2004·Genes & Development·Ping HuNouria Hernandez
Jan 26, 2005·Current Biology : CB·Stéphanie Pellegrin, Harry Mellor
Feb 16, 2005·Nature Structural & Molecular Biology·Alexander KukalevPiergiorgio Percipalle
Jan 19, 2006·The Journal of Cell Biology·Stefan J MarciniakDavid Ron
Mar 22, 2007·Biochemical and Biophysical Research Communications·Shu-Chen KaoHsien-bin Huang
Sep 17, 2008·Molecular and Cellular Biology·Matthew H Brush, Shirish Shenolikar
Oct 22, 2008·Journal of Molecular Biology·Usha B NairKathleen M Trybus
Nov 15, 2008·The EMBO Journal·Stephane MouilleronNeil Q McDonald
Feb 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Heather P HardingDavid Ron
Sep 22, 2009·Methods in Molecular Biology·Andreas Holzinger
Jan 23, 2010·Nature Reviews. Molecular Cell Biology·Richard J JacksonTatyana V Pestova
Mar 23, 2010·Nature Structural & Molecular Biology·Michael J RagusaWolfgang Peti
Feb 15, 2011·Annual Review of Biophysics·Roberto Dominguez, Kenneth C Holmes
Apr 27, 2011·The Journal of Biological Chemistry·Wei ZhouShirish Shenolikar
Jun 26, 2012·Biochemical and Biophysical Research Communications·Kazuyasu ShojiKensaku Mizuno
Mar 13, 2014·American Journal of Respiratory Cell and Molecular Biology·Emily F A van 't WoutStefan J Marciniak
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Margarito RojasThomas E Dever

❮ Previous
Next ❯

Citations

Aug 27, 2016·Annals of the American Thoracic Society·Stefan J MarciniakElke Malzer
Jul 1, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Stefan J Marciniak
Aug 1, 2019·American Journal of Physiology. Cell Physiology·Olesya PlazyoJ-P Jin
Oct 19, 2016·Cytoskeleton·Hermano Martins Bellato, Glaucia Noeli Maroso Hajj
Sep 16, 2016·EMBO Reports·Karolina Pakos-ZebruckaAdrienne M Gorman
Oct 1, 2017·Environmental Science and Pollution Research International·Anthony BertucciMagalie Baudrimont
Oct 27, 2017·International Journal of Molecular Sciences·Ekaterina ChesnokovaPeter Kolosov
Apr 6, 2019·Biological Chemistry·Gisela von HovenNadja Hellmann
Mar 23, 2017·Cellular and Molecular Neurobiology·Dongdong SunJianning Zhang
Apr 6, 2018·The Journal of Biological Chemistry·Ana Crespillo-CasadoDavid Ron
Oct 3, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Giulia EmanuelliStefan J Marciniak
Apr 25, 2020·Science·Mauro Costa-Mattioli, Peter Walter
Feb 15, 2018·Cold Spring Harbor Perspectives in Biology·Ronald C Wek
Sep 6, 2020·The Journal of Biological Chemistry·Julia M D Grandjean, R Luke Wiseman
Mar 28, 2019·Cell Reports·Lauren FigardAnna Marie Sokac
Jan 15, 2021·Life Science Alliance·Andreia MendesPhilippe Pierre
Nov 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tingyu FanJingxing Dai
Mar 2, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Tianxiao HanQingsong Jiang
Nov 7, 2017·Molecular Cell·Claudio Hetz, Feroz R Papa
Aug 26, 2015·Journal of the American Chemical Society·Yu LiuJeffery W Kelly
Oct 10, 2021·Nature Structural & Molecular Biology·Yahui YanDavid Ron
Sep 14, 2021·Molecular and Cellular Biology·Elizabeth L CastleJennifer A Corcoran

❮ Previous
Next ❯

Methods Mentioned

BETA
affinity purification
immunoprecipitation
Fluorescence microscopy
confocal microscopy
pull-downs
immunoprecipitations
Fluorescence
glycosylation
PCR
protein assay

Software Mentioned

ImageJ

Related Concepts

Related Feeds

Actin-binding Proteins

Actin-binding proteins are a component of the actin cytoskeleton that play essential roles in cellular functions such as regulation of actin polymerization, maintenance of cell polarity, gene expression regulation, cell motility and many more functions. Discover the latest research on actin-binding proteins here.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.