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Publication : Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3.

First Author  Sasai M Year  2010
Journal  Science Volume  329
Issue  5998 Pages  1530-4
PubMed ID  20847273 Mgi Jnum  J:163984
Mgi Id  MGI:4830377 Doi  10.1126/science.1187029
Citation  Sasai M, et al. (2010) Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science 329(5998):1530-4
abstractText  Endosomal Toll-like receptors (TLRs) 7 and 9 recognize viral pathogens and induce signals leading to the activation of nuclear factor kappaB (NF-kappaB)-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.
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