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TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88
- Source :
- PLoS ONE, Vol 7, Iss 6, p e38423 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- MyD88, a Toll/interleukin-1 receptor homology (TIR) domain-containing adaptor protein, mediates signals from the Toll-like receptors (TLR) or IL-1/IL-18 receptors to downstream kinases. In MyD88-dependent TLR4 signaling, the function of MyD88 is enhanced by another TIR domain-containing adaptor, Mal/TIRAP, which brings MyD88 to the plasma membrane and promotes its interaction with the cytosolic region of TLR4. Hence, Mal is recognized as the "sorting adaptor" for MyD88. In this study, a direct interaction between MyD88-TIR and another membrane-sorting adaptor, TRAM/TICAM-2, was demonstrated in vitro. Cell-based assays including RNA interference experiments and TRAM deficient mice revealed that the interplay between MyD88 and TRAM in cells is important in mediating IL-18 signal transduction. Live cell imaging further demonstrated the co-localized accumulation of MyD88 and TRAM in the membrane regions in HEK293 cells. These findings suggest that TRAM serves as the sorting adaptor for MyD88 in IL-18 signaling, which then facilitates the signal transduction. The binding sites for TRAM are located in the TIR domain of MyD88 and actually overlap with the binding sites for Mal. MyD88, the multifunctional signaling adaptor that works together with most of the TLR members and with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner in a distinct context.
- Subjects :
- Proteomics
Models, Molecular
TIRAP
lcsh:Medicine
Mice
RNA interference
Receptor
lcsh:Science
Mice, Knockout
Receptors, Interleukin-18
Membrane Glycoproteins
Microscopy, Confocal
Multidisciplinary
Interleukin-18
Signal transducing adaptor protein
hemic and immune systems
Interleukin-12
Innate Immunity
Cell biology
Cytokines
Medicine
RNA Interference
Signal transduction
Research Article
Protein Binding
Signal Transduction
Immunology
Biology
Immune Deficiency
Interferon-gamma
Live cell imaging
Animals
Humans
Immunoprecipitation
Interleukin-18 Receptor beta Subunit
Binding site
Protein Interactions
Adaptor Proteins, Signal Transducing
Binding Sites
HEK 293 cells
lcsh:R
Immunity
Receptors, Interleukin-1
Th1 Cells
Protein Structure, Tertiary
Mice, Inbred C57BL
Toll-Like Receptor 4
HEK293 Cells
Immune System
Mutation
Myeloid Differentiation Factor 88
Clinical Immunology
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....4126e0902ff260954136eb69b15d4c03