Journal Article

DZNE-2020-03408

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA.

Sirois, C. M. ; Jin, T. ; Miller, A. L. ; Bertheloot, D. ; Nakamura, H. ; Horvath, G. L. ; Mian, A. ; Jiang, J. ; Schrum, J. ; Bossaller, L. ; Pelka, K. ; Garbi, N. ; Brewah, Y. ; Tian, J. ; Chang, C. ; Chowdhury, P. S. ; Sims, G. P. ; Kolbeck, R. ; Coyle, A. J. ; Humbles, A. A. ; Xiao, T. S. ; Latz, E. (Last author)DZNE*

2013
Rockefeller Univ. Press New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1084/jem.20120201

Abstract: Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis of RAGE-DNA complexes indicated that DNA interacted with dimers of the outermost RAGE extracellular domains, and could induce formation of higher-order receptor complexes. Furthermore, mice deficient in RAGE were unable to mount a typical inflammatory response to DNA in the lung, indicating that RAGE is important for the detection of nucleic acids in vivo.

Keyword(s): Animals (MeSH) ; Base Sequence (MeSH) ; Cell Membrane: metabolism (MeSH) ; Crystallography, X-Ray (MeSH) ; DNA: chemistry (MeSH) ; DNA: metabolism (MeSH) ; Endocytosis (MeSH) ; Endosomes: metabolism (MeSH) ; HEK293 Cells (MeSH) ; HeLa Cells (MeSH) ; Humans (MeSH) ; Ligands (MeSH) ; Lung: metabolism (MeSH) ; Lung: pathology (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Models, Molecular (MeSH) ; NF-kappa B: metabolism (MeSH) ; Pneumonia: metabolism (MeSH) ; Pneumonia: pathology (MeSH) ; Protein Binding (MeSH) ; Protein Multimerization (MeSH) ; Protein Structure, Tertiary (MeSH) ; Receptor for Advanced Glycation End Products (MeSH) ; Receptors, Immunologic: chemistry (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Static Electricity (MeSH) ; Toll-Like Receptor 9: metabolism (MeSH) ; Ligands ; NF-kappa B ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; Toll-Like Receptor 9 ; DNA

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Contributing Institute(s):

1. Innate Immunity in Neurodegeneration (AG Latz)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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