The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity

Abstract Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling respons...

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Autores principales: Karine Doiron, Vanessa Goyon, Etienne Coyaud, Sanjeeva Rajapakse, Brian Raught, Heidi M. McBride
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:7c05e8c330a54cc0a18d9dbc8e53f90c2021-12-02T16:06:29ZThe dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity10.1038/s41598-017-00151-62045-2322https://doaj.org/article/7c05e8c330a54cc0a18d9dbc8e53f90c2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00151-6https://doaj.org/toc/2045-2322Abstract Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro. A biotin environment scan of MAPL interacting polypeptides identified a series of proteins specific to Sendai virus infection; including RIG-I, IFIT1, IFIT2, HERC5 and others. Upon infection, RIG-I is SUMOylated in a MAPL-dependent manner, a conjugation step that is required for its activation. Consistent with this, MAPL was not required for signaling downstream of a constitutively activated form of RIG-I. These data highlight a critical role for MAPL and mitochondrial SUMOylation in the early steps of antiviral signaling.Karine DoironVanessa GoyonEtienne CoyaudSanjeeva RajapakseBrian RaughtHeidi M. McBrideNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Karine Doiron
Vanessa Goyon
Etienne Coyaud
Sanjeeva Rajapakse
Brian Raught
Heidi M. McBride
The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity
description Abstract Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro. A biotin environment scan of MAPL interacting polypeptides identified a series of proteins specific to Sendai virus infection; including RIG-I, IFIT1, IFIT2, HERC5 and others. Upon infection, RIG-I is SUMOylated in a MAPL-dependent manner, a conjugation step that is required for its activation. Consistent with this, MAPL was not required for signaling downstream of a constitutively activated form of RIG-I. These data highlight a critical role for MAPL and mitochondrial SUMOylation in the early steps of antiviral signaling.
format article
author Karine Doiron
Vanessa Goyon
Etienne Coyaud
Sanjeeva Rajapakse
Brian Raught
Heidi M. McBride
author_facet Karine Doiron
Vanessa Goyon
Etienne Coyaud
Sanjeeva Rajapakse
Brian Raught
Heidi M. McBride
author_sort Karine Doiron
title The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity
title_short The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity
title_full The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity
title_fullStr The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity
title_full_unstemmed The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity
title_sort dynamic interacting landscape of mapl reveals essential functions for sumoylation in innate immunity
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/7c05e8c330a54cc0a18d9dbc8e53f90c
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