Back to Search
Start Over
The CD300e molecule in mice is an immune-activating receptor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2018 Mar 09; Vol. 293 (10), pp. 3793-3805. Date of Electronic Publication: 2018 Jan 22. - Publication Year :
- 2018
-
Abstract
- CD300 molecules (CD300s) belong to paired activating and inhibitory receptor families, which mediate immune responses. Human CD300e (hCD300e) is expressed in monocytes and myeloid dendritic cells and transmits an immune-activating signal by interacting with DNAX-activating protein 12 (DAP12). However, the CD300e ortholog in mice (mCD300e) is poorly characterized. Here, we found that mCD300e is also an immune-activating receptor. We found that mCD300e engagement triggers cytokine production in mCD300e-transduced bone marrow-derived mast cells (BMMCs). Loss of DAP12 and another signaling protein, FcRγ, did not affect surface expression of transduced mCD300e, but abrogated mCD300e-mediated cytokine production in the BMMCs. Co-immunoprecipitation experiments revealed that mCD300e physically interacts with both FcRγ and DAP12, suggesting that mCD300e delivers an activating signal via these two proteins. Binding and reporter assays with the mCD300e extracellular domain identified sphingomyelin as a ligand of both mCD300e and hCD300e. Notably, the binding of sphingomyelin to mCD300e stimulated cytokine production in the transduced BMMCs in an FcRγ- and DAP12-dependent manner. Flow cytometric analysis with an mCD300e-specific Ab disclosed that mCD300e expression is highly restricted to CD115 <superscript>+</superscript> Ly-6C <superscript>low/int</superscript> peripheral blood monocytes, corresponding to CD14 <superscript>dim/+</superscript> CD16 <superscript>+</superscript> human nonclassical and intermediate monocytes. Loss of FcRγ or DAP12 lowered the surface expression of endogenous mCD300e in the CD115 <superscript>+</superscript> Ly-6C <superscript>low/int</superscript> monocytes. Stimulation with sphingomyelin failed to activate the CD115 <superscript>+</superscript> Ly-6C <superscript>low/int</superscript> mouse monocytes, but induced hCD300e-mediated cytokine production in the CD14 <superscript>dim</superscript> CD16 <superscript>+</superscript> human monocytes. Taken together, these observations indicate that mCD300e recognizes sphingomyelin and thereby regulates nonclassical and intermediate monocyte functions through FcRγ and DAP12.<br /> (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Adaptor Proteins, Signal Transducing chemistry
Adaptor Proteins, Signal Transducing genetics
Amino Acid Substitution
Animals
Bone Marrow Cells cytology
Bone Marrow Cells immunology
Bone Marrow Cells metabolism
Cell Line
Cytokines metabolism
Gene Expression Regulation
HEK293 Cells
Humans
Ligands
Mast Cells cytology
Mast Cells immunology
Mice, Inbred C57BL
Mice, Knockout
Monocytes cytology
Monocytes immunology
Mutation
Peptide Fragments agonists
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments metabolism
Protein Interaction Domains and Motifs
Protein Multimerization
Receptors, IgG chemistry
Receptors, IgG genetics
Receptors, Immunologic chemistry
Receptors, Immunologic genetics
Receptors, Immunologic metabolism
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins metabolism
Adaptor Proteins, Signal Transducing metabolism
Mast Cells metabolism
Monocytes metabolism
Protein Processing, Post-Translational
Receptors, IgG metabolism
Receptors, Immunologic agonists
Sphingomyelins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 293
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29358324
- Full Text :
- https://doi.org/10.1074/jbc.RA117.000696