TLR8 dimer FL-TLR9 dimer FL-TLR7 dimer intracellular TLR:UNC93B1 UNC93B1 delivers endosomal full-length TLRs to endolysosome Authored: Shamovsky, V, 2011-10-19 Edited: Shamovsky, V, 2012-02-19 Pubmed14716310 Pubmed15226270 Pubmed16857668 Pubmed18305481 Pubmed21398612 Pubmed21402738 Pubmed9799232 Reactome Database ID Release 431678927 Reactome, http://www.reactome.org ReactomeREACT_118774 Reviewed: Gillespie, ME, 2012-02-09 Reviewed: Leifer, CA, Rose II, WA, 2012-02-28 TLR3, 7, 8 and 9 activation occurs within acidified endolysosomal compartments. Inhibition of endosome acidification with bafilomicin A or chloroquine abrogated TLR's-mediated responses to pathogen-derived nucleic acids (Hacker H et al 1998, Funami K et al 2004, Gibbard RJ et al 2006, Kuznik A et al 2011). Upon stimulation, TLR3, 7, and 9 (and possibly TLR8) are transported to the signaling endosomes by UNC93B1, whereby they become functional receptors and bind to their specific ligands (Kim et al 2008, Ewald et al 2011). Although UNC93B1 is critically involved in TLRs trafficking it was dispensable for ligand binding by these TLRs (Kim YM et al 2008).