Frontline: Carbohydrate-independent recognition of collagens by the macrophage mannose receptor
Frontline: Carbohydrate-independent recognition of collagens by the macrophage mannose receptor
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DOI：
10.1002/eji.200535685
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发表时间：
2006-05-01
影响因子：
5.4
通讯作者：
Gordon, S
中科院分区：
文献类型：
--
作者：
Martinez-Pomares, L;Wienke, D;Gordon, S
甘露糖受体（MR）是具有共同结构域结构的四个内吞分子家族中最具特征的成员；一个富半胱氨酸（CR）结构域，一个纤维连接蛋白II型（FNII）结构域和串联排列的c型凝集素样结构域（CTLD， MR病例中有8个）。mr有两种不同的凝集素活性，CR结构域识别硫酸盐碳水化合物，而CTLD介导与甘露糖、焦糖或n -乙酰氨基葡萄糖的结合。众所周知，FNII结构域对胶原结合很重要，这已经在MR家族的两个成员Endo180和磷脂酶A(2)受体的背景下进行了研究。在这里，我们研究了MR的CR域和CTLD介导的广泛有效的凝集素活性是否有利于损害fnii介导的相互作用(s)。我们发现MR能够以不依赖碳水化合物的方式结合和内化胶原蛋白，MR缺陷的巨噬细胞在IV型胶原蛋白和明胶内化方面有明显缺陷。这些数据在分子水平上具有重要意义，因为现在有三种不同的MR配体结合位点。此外，我们的发现扩大了MR识别的内源性配体的范围，一个分子牢牢地定位在MR。体内平衡和免疫之间的界面。
Mannose receptor (MR) is the best characterised member of a family of four endocytic molecules that share a common domain structure; a cysteine-rich (CR) domain, a fibronectin-type II (FNII) domain and tandemly arranged C-type lectin-like domains (CTLD, eight in the case of MR). Two distinct lectin activities have been described for MR. The CR domain recognises sulphated carbohydrates while the CTLD mediate binding to mannose, fucose or N-acetylglucosamine. FNII domains are known to be important for collagen binding and this has been studied in the context of two members of the MR family, Endo180 and the phospholipase A(2) receptor. Here, we have investigated whether the broad and effective lectin activity mediated by the CR domain and CTLD of MR is favoured to the detriment of FNII-mediated interaction(s). We show that MR is able to bind and internalise collagen in a carbohydrate-independent manner and that MR deficient macrophages have a marked defect in collagen IV and gelatin internalisation. These data have major implications at the molecular level as there are now three distinct ligand-binding sites described for MR. Furthermore our findings extend the range of endogenous ligands recognised by MR, a molecule firmly placed at. the interface between homeostasis and immunity.