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Review
. 2010 Nov 30;3(150):pe45.
doi: 10.1126/scisignal.3150pe45.

Compartment-specific Control of Signaling From a DNA-sensing Immune Receptor

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Review

Compartment-specific Control of Signaling From a DNA-sensing Immune Receptor

Alex Engel et al. Sci Signal. .

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.

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