RRC ID 52880
Author Sasai M, Linehan MM, Iwasaki A.
Title Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3.
Journal Science
Abstract Endosomal Toll-like receptors (TLRs) 7 and 9 recognize viral pathogens and induce signals leading to the activation of nuclear factor κB (NF-κB)-dependent proinflammatory cytokines and interferon regulatory factor 7 (IRF7)-dependent type I interferons (IFNs). Recognition of viral nucleic acids by TLR9 requires its cleavage in the endolysosomal compartment. Here, we show that TLR9 signals leading to the activation of type I IFN, but not proinflammatory cytokine genes, require TLR9 trafficking from endosomes to a specialized lysosome-related organelle. Furthermore, we identify adapter protein-3 as the protein complex responsible for the trafficking of TLR9 to this subcellular compartment. Our results reveal an intracellular mechanism for bifurcation of TLR9 signals by selective receptor trafficking within the endosomal system.
Volume 329(5998)
Pages 1530-4
Published 2010-9-17
DOI 10.1126/science.1187029
PII 329/5998/1530
PMID 20847273
PMC PMC3063333
MeSH Adaptor Protein Complex 3 / genetics Adaptor Protein Complex 3 / metabolism* Adaptor Protein Complex beta Subunits Animals Cells, Cultured Cytokines / genetics Cytokines / immunology Cytokines / metabolism Cytoplasmic Vesicles / metabolism Dendritic Cells / immunology* Dendritic Cells / metabolism Endosomes / metabolism Interferon Regulatory Factor-7 / metabolism Interferon Type I / genetics Interferon Type I / immunology Interferon Type I / metabolism Lysosomal-Associated Membrane Protein 2 / metabolism Macrophages / immunology Membrane Transport Proteins / metabolism Mice Mice, Inbred C57BL Myeloid Differentiation Factor 88 / metabolism Oligodeoxyribonucleotides / immunology Protein Transport Recombinant Fusion Proteins / immunology Recombinant Fusion Proteins / metabolism Signal Transduction TNF Receptor-Associated Factor 3 / metabolism Toll-Like Receptor 9 / immunology Toll-Like Receptor 9 / metabolism* Transcriptional Activation Vesicle-Associated Membrane Protein 3 / metabolism
IF 41.058
DNA material CSII-EF-MCS (RDB04378).