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  The Chaperone UNC93B1 Regulates Toll-like Receptor Stability Independently of Endosomal TLR Transport

Pelka, K., Bertheloot, D., Reimer, E., Phulphagar, K., Schmidt, S. V., Christ, A., et al. (2018). The Chaperone UNC93B1 Regulates Toll-like Receptor Stability Independently of Endosomal TLR Transport. Immunity, 48(5), 911-922.e7. doi:10.1016/j.immuni.2018.04.011.

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 Creators:
Pelka, Karin1, Author
Bertheloot, Damien1, Author
Reimer, Elisa1, Author
Phulphagar, Kshiti1, Author
Schmidt, Susanne V.1, Author
Christ, Anette1, Author
Stahl, Rainer1, Author
Watson, Nicki1, Author
Miyake, Kensuke1, Author
Hacohen, Nir1, Author
Haas, Albert1, Author
Brinkmann, Melanie M.1, Author
Marshak-Rothstein, Ann1, Author
Meissner, Felix2, Author           
Latz, Eicke1, Author
Affiliations:
1external, ou_persistent22              
2Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: ENDOPLASMIC-RETICULUM; DENDRITIC CELLS; PROTEIN UNC93B; NUCLEIC-ACID; LOCALIZATION; RESPONSES; QUANTIFICATION; MACROPHAGES; TRAFFICKING; RECOGNITIONImmunology;
 Abstract: Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5 to the cell surface, raising the question of how UNC93B1 mediates differential TLR trafficking. Here, we report that UNC93B1 regulates a step upstream of the differential TLR trafficking process. We discovered that UNC93B1 deficiency resulted in near-complete loss of TLR3 and TLR7 proteins in primary splenic mouse dendritic cells and macrophages, showing that UNC93B1 is critical for maintaining TLR expression. Notably, expression of an ER-retained UNC93B1 version was sufficient to stabilize TLRs and largely restore endosomal TLR trafficking and activity. These data are critical for an understanding of how UNC93B1 can regulate the function of a broad subset of TLRs.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Issued
 Pages: 19
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Immunity
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 48 (5) Sequence Number: - Start / End Page: 911 - 922.e7 Identifier: ISSN: 1074-7613
CoNE: https://pure.mpg.de/cone/journals/resource/954925604783