UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes
SCIE
SCOPUS
- Title
- UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes
- Authors
- Kim, YM; Brinkmann, MM; Paquet, ME; Ploegh, HL
- Date Issued
- 2008-03-13
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- Signalling by means of toll- like receptors ( TLRs) is essential for the development of innate and adaptive immune responses(1-3). UNC93B1, essential for signalling of TLR3, TLR7 and TLR9 in both humans and mice, physically interacts with these TLRs in the endoplasmic reticulum ( ER)(4-6). Here we show that the function of the polytopic membrane protein UNC93B1 is to deliver the nucleotide- sensing receptors TLR7 and TLR9 from the ER to endolysosomes. In dendritic cells of 3d mice, which express an UNC93B1 missense mutant ( H412R) incapable of TLR binding, neither TLR7 nor TLR9 exits the ER. Furthermore, the trafficking and signalling defects of the nucleotide- sensing TLRs in 3d dendritic cells are corrected by expression of wild- type UNC93B1. However, UNC93B1 is dispensable for ligand recognition and signal initiation by TLRs. To our knowledge, UNC93B1 is the first protein to be identified as a molecule specifically involved in trafficking of nucleotide- sensing TLRs. By inhibiting the interaction between UNC93B1 and TLRs it should be possible to achieve specific regulation of the nucleotide- sensing TLRs without compromising signalling via the cell- surface- disposed TLRs.
- Keywords
- PLASMA-MEMBRANE; CPG-DNA; SUBCELLULAR-LOCALIZATION; EXOGENOUS ANTIGEN; MESSENGER-RNA; PROTEIN; PATHWAY; ER; RECOGNITION; DISTINCT
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/26236
- DOI
- 10.1038/nature06726
- ISSN
- 0028-0836
- Article Type
- Article
- Citation
- NATURE, vol. 452, no. 7184, page. 234 - U80, 2008-03-13
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.