Analyses on the heterodimer formation between different C-type lectin receptors

2014 Fiscal Year Final Research Report

• Project/Area Number: 26670213
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: Kyushu University
• Principal Investigator: YAMASAKI Sho 九州大学, 生体防御医学研究所, 教授 (40312946)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: C型レクチン / 結核菌 / 自然免疫 / パターン認識受容体

Outline of Final Research Achievements

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. 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.

Free Research Field

免疫学