Pelka, Karin, Phulphagar, Kshiti, Zimmermann, Jana, Stahl, Rainer, Schmid-Burgk, Jonathan L., Schmidt, Tobias ORCID: 0000-0003-3102-3515, Spille, Jan-Hendrik ORCID: 0000-0001-8493-4721, Labzin, Larisa I., Agrawal, Sudhir, Kandimalla, Ekambar R., Casanova, Jean-Laurent ORCID: 0000-0002-7782-4169, Hornung, Veit ORCID: 0000-0002-4150-194X, Marshak-Rothstein, Ann, Hoening, Stefan and Latz, Eicke ORCID: 0000-0003-1488-5666 (2014). Cutting Edge: The UNC93B1 Tyrosine-Based Motif Regulates Trafficking and TLR Responses via Separate Mechanisms. J. Immunol., 193 (7). S. 3257 - 3262. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

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Abstract

Sensing of nucleic acids by TLRs is crucial in the host defense against viruses and bacteria. Unc-93 homolog B1 (UNC93B1) regulates the trafficking of nucleic acid-sensing TLRs from the endoplasmic reticulum to endolysosomes, where the TLRs encounter their respective ligands and become activated. In this article, we show that a carboxyl-terminal tyrosine-based sorting motif (Yxx Phi) in UNC93B1 differentially regulates human nucleic acid-sensing TLRs in a receptor-and ligand-specific manner. Destruction of YxxF abolished TLR7, TLR8, and TLR9 activity toward nucleic acids in human B cells and monocytes, whereas TLR8 responses toward small molecules remained intact. YxxF in UNC93B1 influenced the subcellular localization of human UNC93B1 via both adapter protein complex (AP)1- and AP2-dependent trafficking pathways. However, loss of AP function was not causal for altered TLR responses, suggesting AP-independent functions of YxxF in UNC93B1.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pelka, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phulphagar, KshitiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmermann, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stahl, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmid-Burgk, Jonathan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, TobiasUNSPECIFIEDorcid.org/0000-0003-3102-3515UNSPECIFIED
Spille, Jan-HendrikUNSPECIFIEDorcid.org/0000-0001-8493-4721UNSPECIFIED
Labzin, Larisa I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agrawal, SudhirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kandimalla, Ekambar R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Casanova, Jean-LaurentUNSPECIFIEDorcid.org/0000-0002-7782-4169UNSPECIFIED
Hornung, VeitUNSPECIFIEDorcid.org/0000-0002-4150-194XUNSPECIFIED
Marshak-Rothstein, AnnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoening, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Latz, EickeUNSPECIFIEDorcid.org/0000-0003-1488-5666UNSPECIFIED
URN: urn:nbn:de:hbz:38-428134
DOI: 10.4049/jimmunol.1301886
Journal or Publication Title: J. Immunol.
Volume: 193
Number: 7
Page Range: S. 3257 - 3262
Date: 2014
Publisher: AMER ASSOC IMMUNOLOGISTS
Place of Publication: BETHESDA
ISSN: 1550-6606
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NUCLEIC-ACIDS; PROTEINS; RECEPTORS; SIGNALSMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42813

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