Characterization of Leukocyte Mono-immunoglobulin-like Receptor 7 (LMIR7)/CLM-3 as an Activating Receptor ITS SIMILARITIES TO AND DIFFERENCES FROM LMIR4/CLM-5
Characterization of Leukocyte Mono-immunoglobulin-like Receptor 7 (LMIR7)/CLM-3 as an Activating Receptor ITS SIMILARITIES TO AND DIFFERENCES FROM LMIR4/CLM-5
复制标题
DOI：
10.1074/jbc.m110.137166
复制
发表时间：
2010-11-12
影响因子：
4.8
通讯作者：
Kitaura, Jiro
中科院分区：
文献类型：
--
作者：
Enomoto, Yutaka;Yamanishi, Yoshinori;Kitaura, Jiro
在这里，我们表征白细胞单免疫球蛋白样受体7（LMIR 7）/CLM-3，并将其与活化受体LMIR 4/CLM-5进行比较，后者是抑制性受体LMIR 3/CLM-1的对应物。LMIR 7与LMIR 4在其Ig样结构域和跨膜结构域的氨基酸序列上具有高度同源性。流式细胞术分析表明，LMIR 4主要表达在中性粒细胞，而LMIR 7高表达在肥大细胞和单核细胞/巨噬细胞。重要的是，LMIR 7参与诱导骨髓来源的肥大细胞（BMMC）中的细胞因子产生。虽然FcR γ缺陷不影响LMIR 7的表面表达水平，但它消除了LMIR 7介导的BMMC活化。一致地，我们发现LMIR 7-FcR γ的显著相互作用，尽管与LMIR 4-FcR γ相比具有较低的亲和力。我们的研究结果表明，LMIR 7通过与FcR γ相互作用传递激活信号。此外，像LMIR 4一样，LMIR 7在信号传导中与TLR 4协同作用。对LMIR 4和LMIR 7组成的嵌合体受体的分析表明：1）LMIR 7的跨膜区不带电荷，在FcR γ缺失的情况下，LMIR 7的表面表达仍维持在高水平，2）LMIR 7的胞外跨膜区对其表面表达水平有负面影响; LMIR 4与FcR γ的强相互作用依赖于LMIR 4的胞外跨膜区和跨膜结构域。因此，LMIR 7与LMIR 4有相似之处，尽管它们在分布、表达和功能方面受到不同的调节。
Here we characterize leukocyte mono-Ig-like receptor 7 (LMIR7)/CLM-3 and compare it with an activating receptor, LMIR4/CLM-5, that is a counterpart of an inhibitory receptor LMIR3/CLM-1. LMIR7 shares high homology with LMIR4 in the amino acid sequences of its Ig-like and transmembrane domains. Flow cytometric analysis demonstrated that LMIR4 was predominantly expressed in neutrophils, whereas LMIR7 was highly expressed in mast cells and monocytes/macrophages. Importantly, LMIR7 engagement induced cytokine production in bone marrow-derived mast cells (BMMCs). Although FcR gamma deficiency did not affect surface expression levels of LMIR7, it abolished LMIR7-mediated activation of BMMCs. Consistently we found significant interaction of LMIR7-FcR gamma, albeit with lower affinity compared with that of LMIR4-FcR gamma. Our results showed that LMIR7 transmits an activating signal through interaction with FcR gamma. In addition, like LMIR4, LMIR7 synergizes with TLR4 in signaling. Analysis of several chimera receptors composed of LMIR4 and LMIR7 revealed these findings: 1) the transmembrane of LMIR7 with no charged residues maintained its surface expression at high levels in the absence of FcR gamma; 2) the extracellular juxtamembrane region of LMIR7 had a negative effect on its surface expression levels; and 3) the strong interaction of LMIR4 with FcR gamma depended on the extracellular juxtamembrane region as well as the transmembrane domain of LMIR4. Thus, LMIR7 shares similarities with LMIR4, although they are differentially regulated in their distribution, expression, and function.