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

Karine Doiron; Vanessa Goyon; Etienne Coyaud; Sanjeeva Rajapakse; Brian Raught; Heidi M McBride

doi:10.1038/s41598-017-00151-6

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

Sci Rep. 2017 Mar 7;7(1):107. doi: 10.1038/s41598-017-00151-6.

Authors

Karine Doiron¹, Vanessa Goyon¹, Etienne Coyaud², Sanjeeva Rajapakse¹, Brian Raught^{2

3}, Heidi M McBride⁴

Affiliations

¹ Montreal Neurological Institute, McGill University, 3801 University Ave, Montreal, Quebec, H3A 2B4, Canada.
² Princess Margaret Cancer Centre, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada.
³ Department of Medical Biophysics, University of Toronto, Toronto, Canada.
⁴ Montreal Neurological Institute, McGill University, 3801 University Ave, Montreal, Quebec, H3A 2B4, Canada. Heidi.mcbride@mcgill.ca.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Apoptosis Regulatory Proteins
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cells, Cultured
Immunity, Innate*
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Mice
Protein Interaction Mapping
Proteins / genetics
Proteins / metabolism
RNA-Binding Proteins
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism*
Respirovirus Infections / genetics*
Respirovirus Infections / metabolism
Respirovirus Infections / virology
Sendai virus / pathogenicity*
Signal Transduction
Sumoylation
Transcriptional Activation
Ubiquitin-Protein Ligases / metabolism*

Substances

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
Carrier Proteins
HERC5 protein, human
IFIT1 protein, human
IFIT2 protein, human
Intracellular Signaling Peptides and Proteins
PLAAT4 protein, human
Proteins
RNA-Binding Proteins
Receptors, Retinoic Acid
MUL1 protein, human
Ubiquitin-Protein Ligases

Grants and funding

CIHR/Canada