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SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages.
- Source :
-
The Journal of cell biology [J Cell Biol] 2018 Apr 02; Vol. 217 (4), pp. 1411-1429. Date of Electronic Publication: 2018 Feb 12. - Publication Year :
- 2018
-
Abstract
- Signaling lymphocytic activation molecule family 1 (SLAMF1) is an Ig-like receptor and a costimulatory molecule that initiates signal transduction networks in a variety of immune cells. In this study, we report that SLAMF1 is required for Toll-like receptor 4 (TLR4)-mediated induction of interferon β (IFNβ) and for killing of Gram-negative bacteria by human macrophages. We found that SLAMF1 controls trafficking of the Toll receptor-associated molecule (TRAM) from the endocytic recycling compartment (ERC) to Escherichia coli phagosomes. In resting macrophages, SLAMF1 is localized to ERC, but upon addition of E. coli , it is trafficked together with TRAM from ERC to E. coli phagosomes in a Rab11-dependent manner. We found that endogenous SLAMF1 protein interacted with TRAM and defined key interaction domains as amino acids 68 to 95 of TRAM as well as 15 C-terminal amino acids of SLAMF1. Interestingly, the SLAMF1-TRAM interaction was observed for human but not mouse proteins. Overall, our observations suggest that SLAMF1 is a new target for modulation of TLR4-TRAM-TRIF inflammatory signaling in human cells.<br /> (© 2018 Yurchenko et al.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing immunology
Adaptor Proteins, Vesicular Transport genetics
Adaptor Proteins, Vesicular Transport immunology
Animals
Endosomes drug effects
Endosomes immunology
Endosomes microbiology
Escherichia coli metabolism
Escherichia coli pathogenicity
HEK293 Cells
Host-Pathogen Interactions
Humans
Interferon Regulatory Factor-3 metabolism
Interferon-beta genetics
Interferon-beta metabolism
Lipopolysaccharides pharmacology
Macrophages drug effects
Macrophages immunology
Macrophages microbiology
Male
Mice, Inbred C57BL
Mice, Knockout
Phagosomes metabolism
Protein Binding
Protein Interaction Domains and Motifs
Protein Serine-Threonine Kinases metabolism
Protein Transport
Signal Transduction
Signaling Lymphocytic Activation Molecule Family Member 1 genetics
Signaling Lymphocytic Activation Molecule Family Member 1 immunology
THP-1 Cells
Toll-Like Receptor 4 genetics
Toll-Like Receptor 4 immunology
rab GTP-Binding Proteins genetics
rab GTP-Binding Proteins metabolism
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Vesicular Transport metabolism
Endosomes metabolism
Macrophage Activation drug effects
Macrophages metabolism
Signaling Lymphocytic Activation Molecule Family Member 1 metabolism
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 217
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 29440514
- Full Text :
- https://doi.org/10.1083/jcb.201707027