UNC93B1 delivers endosomal full-length TLRs to endolysosome

Stable Identifier
Reaction [omitted]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
14716310 TLR9 signals after translocating from the ER to CpG DNA in the lysosome

Latz, E, Schoenemeyer, A, Visintin, A, Fitzgerald, KA, Monks, BG, Knetter, CF, Lien, E, Nilsen, NJ, Espevik, T, Golenbock, DT

Nat Immunol 2004
16857668 Conserved features in the extracellular domain of human toll-like receptor 8 are essential for pH-dependent signaling

Gibbard, RJ, Morley, PJ, Gay, NJ

J Biol Chem 2006
9799232 CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation

Hacker, H, Mischak, H, Miethke, T, Liptay, S, Schmid, R, Sparwasser, T, Heeg, K, Lipford, GB, Wagner, H

EMBO J 1998
15226270 The cytoplasmic 'linker region' in Toll-like receptor 3 controls receptor localization and signaling

Funami, K, Matsumoto, M, Oshiumi, H, Akazawa, T, Yamamoto, A, Seya, T

Int Immunol 2004
18305481 UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes

Kim, YM, Brinkmann, MM, Paquet, ME, Ploegh, HL

Nature 2008
21402738 Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase

Ewald, SE, Engel, A, Lee, J, Wang, M, Bogyo, M, Barton, GM

J Exp Med 2011
21398612 Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines

Kuznik, A, Bencina, M, Svajger, U, Jeras, M, Rozman, B, Jerala, R

J Immunol 2011
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