Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis

Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis
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DOI:
10.1006/geno.2002.6745
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发表时间:
2002-04-01
期刊:
影响因子:
4.4
通讯作者:
Bicknell, R
Bicknell, R
中科院分区:
生物学3区
文献类型:
--
作者:
Huminiecki, L;Gorn, M;Bicknell, R

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我们利用生物信息学数据挖掘技术鉴定出一个新的内皮特异性基因,它编码的一种蛋白质与轴突导向蛋白“绕道”(ROBO1)具有同源性。这个新基因被称为“神奇绕道”(ROBO4;基因库登录号AF361473),且比“绕道”基因家族的其他成员要小。因此,在细胞外区域,“神奇绕道”仅具有其他“绕道”基因中5个免疫球蛋白结构域中的2个以及3个纤连蛋白结构域中的2个。在体外,仅在内皮细胞中检测到“神奇绕道”的表达,且在缺氧环境下的细胞中表达量更高。原位杂交和免疫组织化学验证了生物信息学的预测,即“神奇绕道”在体内的表达具有内皮特异性。在成年个体中,“神奇绕道”的表达仅局限于活跃的血管生成部位,尤其是肿瘤血管。“神奇绕道”的鉴定表明,“绕道”基因家族的作用范围超出了神经组织,并且“绕道”/“狭缝”相互作用可能在血管生成中起作用。
We have used bioinformatic data mining to identify a novel, endothelial-specific gene encoding a protein with homology to the axon guidance protein roundabout (ROBO1). The new gene has been called magic roundabout (ROBO4; GenBank acc. no. AF361473) and is smaller than other members of the roundabout gene family. Thus, in the extracellular region, magic roundabout has only two of the five immunoglobulin and two of the three fibronectin domains present in other roundabout genes. Expression of magic roundabout in vitro was detected in only endothelial cells and was greater in cells exposed to hypoxia. In situ hybridization and immunohistochemistry validated the bioinformatic prediction that magic roundabout expression would be endothelial specific in vivo. Magic roundabout expression in the adult was restricted exclusively to sites of active angiogenesis, notably tumor vessels. The identification of magic roundabout shows that the roundabout gene family extends beyond neuronal tissue and that roundabout/slit interactions are likely to have a role in angiogenesis.