A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction.

ABSTRACT: The Toll-like receptors (TLRs) of the innate immune system are unusual in that individual family members are located on different organelles, yet most activate a common signaling pathway important for host defense. It remains unclear how this common signaling pathway can be activated from multiple subcellular locations. Here, we report that, in response to natural activators of innate immunity, the sorting adaptor TIRAP regulates TLR signaling from the plasma membrane and endosomes. TLR signaling from both locations triggers the TIRAP-dependent assembly of the myddosome, a protein complex that controls proinflammatory cytokine expression. The actions of TIRAP depend on the promiscuity of its phosphoinositide-binding domain. Different lipid targets of this domain direct TIRAP to different o

SUBMITTER: Bonham KS 

PROVIDER: S-EPMC3951743 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature