Stress granules regulate double-stranded RNA-dependent protein kinase activation through a complex containing G3BP1 and Caprin1

MBio
Lucas C ReinekeRichard E Lloyd

Abstract

Stress granules (SGs) are dynamic cytoplasmic repositories containing translationally silenced mRNAs that assemble upon cellular stress. We recently reported that the SG nucleating protein G3BP1 promotes antiviral activity and is essential in double-stranded RNA-dependent protein kinase (PKR) recruitment to stress granules, thereby driving phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we delineate the mechanism for SG-dependent PKR activation. We show that G3BP1 and inactive PKR directly interact with each other, dependent on both the NTF2-like and PXXP domains of G3BP1. The G3BP1-interacting protein Caprin1 also directly interacts with PKR, regulates efficient PKR activation at the stress granule, and is also integral for the release of active PKR into the cytoplasm to engage in substrate recognition. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. Our data links stress responses and their resultant SGs with innate immune activation through PKR without a requirement for foreign double-stranded RNA (dsRNA) pattern recognition. Our previous work indicates that stress granules have a...Continue Reading

References

Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·T G LeeM G Katze
Aug 4, 1998·The EMBO Journal·R C Patel, G C Sen
Mar 10, 2001·Molecular and Cellular Biology·G A PetersG C Sen
Mar 19, 2003·The Journal of Cell Biology·Helene TourrièreJamal Tazi
Nov 30, 2004·Journal of Molecular Biology·Peter A LemaireJames L Cole
Apr 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Abujiang PataerStephen G Swisher
Jun 22, 2005·The Journal of Cell Biology·Nancy KedershaPaul Anderson
Sep 17, 2005·Molecular and Cellular Biology·Latifa ZekriJamal Tazi
May 18, 2006·Virus Research·Jeffrey O LanglandBertram L Jacobs
May 24, 2006·Emerging Infectious Diseases·Indrawati SendowPeter Daniels
Dec 13, 2006·Microbiology and Molecular Biology Reviews : MMBR·M A GarcíaM Esteban
Jan 2, 2007·Trends in Biochemical Sciences·James L Cole
Nov 17, 2007·Cell Host & Microbe·James P WhiteRichard E Lloyd
Dec 22, 2007·Nucleic Acids Research·Megan MittelstadtRekha C Patel
Sep 24, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nobuyuki ShiinaMakio Tokunaga
Dec 15, 2010·Journal of Virology·M Simpson-HolleyJ H Connor
Jun 24, 2011·Journal of Virology·James P WhiteRichard E Lloyd
Jul 15, 2011·Journal of Virology·Fabian Borghese, Thomas Michiels
Dec 29, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Denys A KhaperskyyCraig McCormick
Mar 13, 2012·Trends in Microbiology·James P White, Richard E Lloyd
Jul 27, 2012·Molecular Biology of the Cell·Lucas C ReinekeRichard E Lloyd
Dec 12, 2012·Molecular and Cellular Biology·Masahiko TakahashiMasahiro Fujii
Jan 8, 2013·Virology·Lucas C Reineke, Richard E Lloyd
Mar 29, 2013·Journal of Virology·Martijn A LangereisFrank J van Kuppeveld
Mar 14, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xi WenHonglin Chen
Jul 11, 2014·PLoS Pathogens·Denys A KhaperskyyCraig McCormick
Aug 5, 2014·Cytokine & Growth Factor Reviews·Qian FengFrank J M van Kuppeveld

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Citations

Nov 28, 2015·Viruses·Jonathan D DoughertyRichard E Lloyd
Mar 22, 2016·Viruses·Renée L Finnen, Bruce W Banfield
Mar 30, 2016·The Journal of Cell Biology·Nancy KedershaPaul Anderson
Jun 25, 2016·Viruses·Susana LópezCarlos Sandoval-Jaime
Jun 13, 2016·Trends in Cell Biology·David S W Protter, Roy Parker
Jul 2, 2016·Viruses·Natalia Poblete-DuránFernando Valiente-Echeverría
Dec 22, 2016·Viruses·Wendy Ullmer, Bert L Semler
Apr 11, 2017·Journal of Theoretical Biology·Wylie Stroberg, Santiago Schnell
Oct 31, 2017·PLoS Pathogens·Nishi R SharmaZhi-Ming Zheng
Jul 30, 2017·The FEBS Journal·Alfonso GalanEncarnacion Martinez-Salas
Sep 7, 2018·Journal of Cell Science·Lucas C ReinekeJoel R Neilson
Nov 9, 2018·Journal of Virology·Linda J VisserFrank J M van Kuppeveld
Aug 8, 2018·Cold Spring Harbor Perspectives in Biology·Pavel IvanovPaul Anderson
May 1, 2019·Virologica Sinica·Qiang ZhangMingzhou Chen
Jun 25, 2019·Wiley Interdisciplinary Reviews. RNA·Yong Sun LeeYeon-Su Lee
Jul 12, 2019·Journal of Virology·Fabian BorgheseThomas Michiels
Apr 17, 2020·Journal of Virology·Praveen ManivannanKrishnamurthy Malathi
Jun 12, 2020·The FEBS Journal·Mohamed S TahaMohammad R Ahmadian
Jun 21, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sean M Cascarina, Eric D Ross
Sep 8, 2016·The Journal of Biological Chemistry·Wei-Chih TsaiRichard E Lloyd
Nov 5, 2019·Frontiers in Cellular and Infection Microbiology·Aracelly Gaete-ArgelFernando Valiente-Echeverría
Jul 14, 2017·Frontiers in Cellular and Infection Microbiology·Yu-Hsiu ChangJim-Tong Horng
Jan 24, 2018·Immunology and Cell Biology·Hazel QuekTara L Roberts
Nov 21, 2018·Life Science Alliance·Aala A AbulfarajNaganand Rayapuram
May 20, 2020·Viruses·Matthew J BrownswordHelena J Maier
Jul 4, 2017·Nature Reviews. Immunology·Craig McCormick, Denys A Khaperskyy

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Methods Mentioned

BETA
immunoprecipitation
pulldown
transfections
transfection

Software Mentioned

ImageJ

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