TY - JOUR
T1 - The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling
AU - Brinkmann, Melanie M.
AU - Spooner, Eric
AU - Hoebe, Kasper
AU - Beutler, Bruce
AU - Ploegh, Hidde L.
AU - Kim, You Me
PY - 2007/4/23
Y1 - 2007/4/23
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.200612056
DO - 10.1083/jcb.200612056
M3 - Article
C2 - 17452530
AN - SCOPUS:34247484007
SN - 0021-9525
VL - 177
SP - 265
EP - 275
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -