Reactome | UNC93B1 delivers endosomal full-length TLRs to endolysosome

UNC93B1 delivers endosomal full-length TLRs to endolysosome

Stable Identifier

R-HSA-1678927

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

endolysosome membrane, Golgi membrane

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UNC93B1 delivers endosomal full-length TLRs to endolysosome

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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