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Sci. Signal., 30 November 2010
Vol. 3, Issue 150, p. pe45
[DOI: 10.1126/scisignal.3150pe45]

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Compartment-Specific Control of Signaling from a DNA-Sensing Immune Receptor

Alex Engel and Gregory M. Barton*

Division of Immunology and Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA.

Abstract: Many cell signaling events are spatially organized, enabling control of specificity, amplitude, and duration. Toll-like receptor 9 (TLR9) binds to nucleic acid sequences present in bacteria or DNA viruses and initiates a signaling pathway that culminates in the transcriptional induction of genes important for host defense, such as those encoding proinflammatory cytokines and type I interferon. A specialized membrane trafficking pathway has been described that is required for a specific branch of TLR9 signaling: the production of type I interferon. Cells deficient for the clathrin adaptor complex AP-3 failed to traffic TLR9 to a specific endosomal compartment and were unable to produce type I interferon despite normal increases in the abundance of interleukin-12p40, a proinflammatory cytokine. These findings support a model in which the targets of TLR9 engagement are controlled by the compartment in which TLR9 is activated.

* Corresponding author. E-mail, barton{at}berkeley.edu

Citation: A. Engel, G. M. Barton, Compartment-Specific Control of Signaling from a DNA-Sensing Immune Receptor. Sci. Signal. 3, pe45 (2010).

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