The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling

Melanie M. Brinkmann, Eric Spooner, Kasper Hoebe, Bruce Beutler, Hidde L. Ploegh, You Me Kim

Research output: Contribution to journalArticle

321 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) sense the presence of microbial and viral pathogens by signal transduction mechanisms that remain to be fully elucidated. A single point mutation (H412R) in the polytopic endoplasmic reticulum (ER)-resident membrane protein UNC93B abolishes signaling via TLR3, 7, and 9. We show that UNC93B specifically interacts with TLR3, 7, 9, and 13, whereas introduction of the point mutation H412R in UNC93B abolishes their interactions. We establish the physical interaction of the intracellular TLRs with UNC93B in splenocytes and bone marrow-derived dendritic cells. Further, by expressing chimeric TLRs, we show that TLR3 and 9 bind to UNC93B via their transmembrane domains. We propose that a physical association between UNC93B and TLRs in the ER is essential for proper TLR signaling.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalJournal of Cell Biology
Volume177
Issue number2
DOIs
StatePublished - Apr 23 2007

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Toll-Like Receptors
Endoplasmic Reticulum
Membrane Proteins
Point Mutation
Dendritic Cells
Signal Transduction
Bone Marrow

ASJC Scopus subject areas

  • Cell Biology

Cite this

The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. / Brinkmann, Melanie M.; Spooner, Eric; Hoebe, Kasper; Beutler, Bruce; Ploegh, Hidde L.; Kim, You Me.

In: Journal of Cell Biology, Vol. 177, No. 2, 23.04.2007, p. 265-275.

Research output: Contribution to journalArticle

Brinkmann, Melanie M. ; Spooner, Eric ; Hoebe, Kasper ; Beutler, Bruce ; Ploegh, Hidde L. ; Kim, You Me. / The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. In: Journal of Cell Biology. 2007 ; Vol. 177, No. 2. pp. 265-275.
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