Data explaining how a single sensor of 'danger' manages to activate two distinct host immune defense signaling pathways is presented in a paper published online in Nature Immunology. TLR4, a detector of a bacterial component, triggers activation of a signaling pathway culminating in production of type I interferon -- a protein that elicits a state of immune system 'alert' -- and of a signaling cascade eliciting other pro-inflammatory signaling molecules. Unlike other type I interferon-inducing receptors, which reside inside immune cells, TLR4 sits on the surface of immune cells.
Ruslan Medzhitov and colleagues show that TRAM, a protein that binds the intracellular tail of TLR4, routes TLR4 from the cell surface to intracellular compartments. This TRAM-mediated trafficking allows TLR4 to 'multi-task' by sequentially activating two signaling pathways -- first one from the cell surface and then a second from within the cell interior.
Ruslan Medzhitov (Yale University School of Medicine, New Haven, Connecticut, USA)
Abstract available online.
(C) Nature Immunology press release.
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