title: 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 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.
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Ave, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Doiron
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Ave, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Goyon
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada.
authors.forename: Etienne
authors.initials: E
authors.lastname: Coyaud
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Ave, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Sanjeeva
authors.initials: S
authors.lastname: Rajapakse
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Ave, Montreal, Quebec, H3A 2B4, Canada. Heidi.mcbride@mcgill.ca.
authors.forename: Heidi M
authors.identifier: 0000-0003-4666-2280
authors.initials: HM
authors.lastname: McBride
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D010253:Respirovirus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D029082:Sendai virus / Q000472:pathogenicity*; D015398:Signal Transduction; D058207:Sumoylation; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C402395:HERC5 protein, human; C484290:IFIT1 protein, human; C484289:IFIT2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C437968:PLAAT4 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D018168:Receptors, Retinoic Acid; C529067:MUL1 protein, human; D044767:Ubiquitin-Protein Ligases