Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response

RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and r...

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Bibliographic Details
Published in:Scientific reports 2017-09, Vol.7 (1), p.11905-13, Article 11905
Main Authors: Kouwaki, Takahisa, Okamoto, Masaaki, Tsukamoto, Hirotake, Fukushima, Yoshimi, Matsumoto, Misako, Seya, Tsukasa, Oshiumi, Hiroyuki
Format: Article
Language:English
Subjects:
13/1
13/109
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38/77
631/250/262/2106/2518
631/326/596/2553
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Adaptor Proteins, Signal Transducing - metabolism
Caspase
DEAD Box Protein 58 - metabolism
Ectopic expression
HEK293 Cells
HeLa Cells
Humanities and Social Sciences
Humans
Immune response
Inflammation
Influenza A
Innate immunity
Interferon
Interferon-beta - genetics
Mitochondria
multidisciplinary
Oligomerization
Polyinosinic:polycytidylic acid
Promoter Regions, Genetic
Protein Binding
Protein Interaction Maps
Receptors, Immunologic
Ribonucleic acid
RNA
RNA viruses
Science
Science (multidisciplinary)
Yeasts
Zyxin - metabolism
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Summary:RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin co-immunoprecipitated with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-β promoter activation, and knockdown of zyxin ( ZYX ) attenuated the IFN-β promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with polyI:C or influenza A virus RNA. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-12224-7