当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1-IRF3 signaling axis.

MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1-IRF3 signaling axis.

Abstract：

:The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling. Depletion of BTN3A1 inhibits the cytoplasmic nucleic acid- or virus-triggered activation of IFN-β production. In the resting state, BTN3A1 is constitutively associated with TBK1. Stimulation with nucleic acids induces the redistribution of the BTN3A1-TBK1 complex to the perinuclear region, where BTN3A1 mediates the interaction between TBK1 and IRF3, leading to the phosphorylation of IRF3. Furthermore, we show that microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. Our findings demonstrate a critical role for MAP4 and BTN3A1 in the spatiotemporal regulation of TBK1, a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Seo M,Lee SO,Kim JH,Hong Y,Kim S,Kim Y,Min DH,Kong YY,Shin J,Ahn K

doi

10.1073/pnas.1615287113

subject

Has Abstract

pub_date

2016-12-13 00:00:00

pages

14390-14395

issue

50

eissn

0027-8424

issn

1091-6490

pii

1615287113

journal_volume

113

pub_type

杂志文章

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