The zinc-finger protein ZFYVE1 modulates TLR3-mediated signaling by facilitating TLR3 ligand binding.

Cellular & Molecular Immunology
Xuan ZhongHong-Bing Shu

Abstract

Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to the induction of downstream antiviral effectors and the innate antiviral immune response. Here, we identified the zinc-finger FYVE domain-containing protein ZFYVE1, a guanylate-binding protein (GBP), as a positive regulator of TLR3-mediated signaling. Overexpression of ZFYVE1 promoted the transcription of downstream antiviral genes upon stimulation with the synthetic TLR3 ligand poly(I:C). Conversely, ZFYVE1 deficiency had the opposite effect. Zfyve1-/- mice were less susceptible than wild-type mice to inflammatory death induced by poly(I:C) but not LPS. ZFYVE1 was associated with TLR3, and the FYVE domain of ZFYVE1 and the ectodomain of TLR3 were shown to be responsible for their interaction. ZFYVE1 was bound to poly(I:C) and increased the binding affinity of TLR3 to poly(I:C). These findings suggest that ZFYVE1 plays an important role in the TLR3-mediated innate immune and inflammatory responses by promoting the ligand binding of TLR3.

References

Sep 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Misako MatsumotoTsukasa Seya
May 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jessica K BellDavid M Segal
Jul 22, 2006·The EMBO Journal·Ingvild Bjellmo JohnsenMarit W Anthonsen
Mar 20, 2009·Proteins·Ju HeTatiana G Kutateladze
Sep 24, 2010·The Journal of Biological Chemistry·Yan WangDavid M Segal
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alejandra Garcia-CattaneoPhilippe Benaroch
Jul 20, 2012·Science Signaling·Michifumi YamashitaGanes C Sen
Aug 7, 2012·The Journal of Biological Chemistry·Rongsu QiC Cheng Kao
Dec 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florent ToscanoSerge Lebecque
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Mar 5, 2015·EMBO Reports·Yun-Hong HuYu Liu
Apr 17, 2015·Biomedical Research·Tomohisa NanaoYasuo Uchiyama
Mar 5, 2016·Cell Research·Shu ZhuRichard A Flavell
Dec 27, 2016·Journal of the Neurological Sciences·Rajesh Verma, Kavita Bharti
Feb 15, 2017·Cellular & Molecular Immunology·Ming-Ming Hu, Hong-Bing Shu
Feb 13, 2018·Cellular & Molecular Immunology·Ying LiuShu Li
Feb 20, 2018·Cellular & Molecular Immunology·Wei-Wei Luo, Hong-Bing Shu
Aug 24, 2018·Nature Communications·Huan LianHong-Bing Shu
Nov 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Heng LinHong-Bing Shu

❮ Previous
Next ❯

Citations

Jun 19, 2021·The Journal of Clinical Endocrinology and Metabolism·Cheuk Wun LiYaron Tomer
Aug 21, 2021·Journal of Zhejiang University. Science. B·Yujuan ChenHuashan Yi

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
PCR
ELISA
coimmunoprecipitation
confocal microscopy
microscale thermophoresis
pulldown
genotyping
transfection
immunoprecipitation
flow cytometry

Software Mentioned

NanoTemper Analysis
Excel
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.