Article ; Online: C-Type Lectin Receptor MCL Facilitates Mincle Expression and Signaling through Complex Formation.
Journal of immunology (Baltimore, Md. : 1950)
2015 Volume 194, Issue 11, Page(s) 5366–5374
Abstract: C-type lectin receptors expressed in APCs are recently defined pattern recognition receptors that play a crucial role in immune responses against pathogen-associated molecular patterns. Among pathogen-associated molecular patterns, cord factor (trehalose- ...
| Abstract | C-type lectin receptors expressed in APCs are recently defined pattern recognition receptors that play a crucial role in immune responses against pathogen-associated molecular patterns. Among pathogen-associated molecular patterns, cord factor (trehalose-6,6'-dimycolate [TDM]) is the most potent immunostimulatory component of the mycobacterial cell wall. Two C-type lectin receptors, macrophage-inducible C-type lectin (Mincle) and macrophage C-type lectin (MCL), are required for immune responses against TDM. Previous studies indicate that MCL is required for TDM-induced Mincle expression. However, the mechanism by which MCL induces Mincle expression has not been fully understood. In this study, we demonstrate that MCL interacts with Mincle to promote its surface expression. After LPS or zymosan stimulation, MCL-deficient bone marrow-derived dendritic cells (BMDCs) had a lower level of Mincle protein expression, although mRNA expression was comparable with wild-type BMDCs. Meanwhile, BMDCs from MCL transgenic mice showed an enhanced level of Mincle expression on the cell surface. MCL was associated with Mincle through the stalk region and this region was necessary and sufficient for the enhancement of Mincle expression. This interaction appeared to be mediated by the hydrophobic repeat of MCL, as substitution of four hydrophobic residues within the stalk region with serine (MCL(4S)) abolished the function to enhance the surface expression of Mincle. MCL(4S) mutant failed to restore the defective TDM responses in MCL-deficient BMDCs. These results suggest that MCL positively regulates Mincle expression through protein-protein interaction via its stalk region, thereby magnifying Mincle-mediated signaling. |
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| MeSH term(s) | Amino Acid Sequence ; Animals ; Bone Marrow Cells/immunology ; Cell Wall/immunology ; Cells, Cultured ; Cord Factors/immunology ; Dendritic Cells/immunology ; Hydrophobic and Hydrophilic Interactions ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Lipopolysaccharides/immunology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Mycobacterium tuberculosis/immunology ; Protein Interaction Domains and Motifs/immunology ; Protein Structure, Tertiary ; RNA, Messenger/biosynthesis ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Signal Transduction ; Tuberculosis/immunology ; Zymosan/immunology | ||||||||||
| Chemical Substances | Clec4d protein, mouse ; Clecsf8 protein, mouse ; Cord Factors ; Lectins, C-Type ; Lipopolysaccharides ; Membrane Proteins ; RNA, Messenger ; Receptors, Immunologic ; Zymosan (9010-72-4) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2015-06-01 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 3056-9 | ||||||||||
| ISSN | 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| ISSN (online) | 1550-6606 | ||||||||||
| ISSN | 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| DOI | 10.4049/jimmunol.1402429 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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