Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ
Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ
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DOI：
10.1002/eji.201343752
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发表时间：
2013-12-01
影响因子：
5.4
通讯作者：
Daws, Michael R.
中科院分区：
文献类型：
--
作者：
Lobato-Pascual, Ana;Saether, Per Christian;Daws, Michael R.
在受体活化后，髓样C型凝集素受体Mincle通过Syk-CARD 9-Bcl 10-MALT 1途径发出信号。它通过募集携带ITAM的Fc β RI-来实现。相关受体巨噬细胞C型凝集素（MCL）也已被证明与Syk相关，并依赖于该信号传导轴。我们以前已经表明，MCL与Fc β RI-共沉淀，但不能显示直接关联，表明MCL与Fc β RI-通过另一种分子关联。在这里，我们使用大鼠原代细胞和细胞系来研究这个缺失的环节。流式细胞仪和生化分析的组合表明，Mincle和MCL形成异聚体的细胞表面上。此外，与MCL和Fc β RI的结合增加了Mincle表达并增强了Ab包被珠的吞噬作用。本文提出的结果表明，Mincle/MCL/Fc β RI-复合物是骨髓细胞表面上这些C型凝集素受体的功能最佳形式。
Upon receptor activation, the myeloid C-type lectin receptor Mincle signals via the Syk-CARD9-Bcl10-MALT1 pathway. It does so by recruiting the ITAM-bearing Fc epsilon RI-. The related receptor macrophage C-type Lectin (MCL) has also been shown to be associated with Syk and to be dependent upon this signaling axis. We have previously shown that MCL co-precipitates with Fc epsilon RI-, but were unable to show a direct association, suggesting that MCL associates with Fc epsilon RI- via another molecule. Here, we have used rat primary cells and cell lines to investigate this missing link. A combination of flow cytometric and biochemical analysis showed that Mincle and MCL form heteromers on the cell surface. Furthermore, association with MCL and Fc epsilon RI- increased Mincle expression and enhanced phagocytosis of Ab-coated beads. The results presented in this paper suggest that the Mincle/MCL/Fc epsilon RI- complex is the functionally optimal form for these C-type lectin receptors on the surface of myeloid cells.