Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion
Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion
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DOI：
10.1016/s0169-328x(00)00108-x
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发表时间：
2000-06-23
期刊：
影响因子：
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通讯作者：
Yamakawa, K
中科院分区：
文献类型：
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作者：
Agarwala, KL;Nakamura, S;Yamakawa, K
由 21 三体引起的唐氏综合症 (DS) 是与智力低下相关的最常见的出生缺陷。最近，在 DS 关键区域中发现了一个名为 DSCAM 的新基因。 DSCAM预计是一种跨膜蛋白，与细胞粘附分子IE超家族具有非常高的结构和序列同源性，并且在发育中的神经系统中表达，在胎儿大脑中表达水平最高。细胞表面和细胞外基质的多种糖蛋白在操作上被称为“粘附分子”，对于神经系统发育、维持和再生过程中细胞相互作用的规范非常重要。为了了解 DSCAM 蛋白的细胞功能，我们将人 DSCAM cDNA 转染至小鼠成纤维细胞 L 细胞中并分析其表达。在蛋白质印迹分析中，针对重组 DSCAM-Ig3 产生的抗体识别出 DSCAM 转染的 L 细胞膜部分中的 198 kDa 蛋白条带。表达 DSCAM 的稳定转化体表现出均匀的表面表达。表达 DSCAM 的转染子表现出增强的粘附特性，以更快的动力学聚集并以同质方式形成聚集体。这种细胞聚集不需要二价阳离子。这些结果证明 DSCAM 是一种细胞粘附分子，可以介导 DSCAM 表达细胞之间的不依赖于阳离子的同亲结合活性。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Down Syndrome (DS) caused by trisomy 21 is the most common birth defect associated with mental retardation. Recently, a novel gene named, DSCAM, has been identified in the DS critical region. DSCAM is predicted to be a transmembrane protein with a very high structural and sequence homology to IE superfamily of cell adhesion molecules and is expressed in the developing nervous system with the highest level in fetal brain. Diverse glycoproteins of cell surfaces and extracellular matrices operationally termed as 'adhesion molecule' are important in the specification of cell interactions during development, maintenance and regeneration of the nervous system. To understand the cellular function of DSCAM protein, we transfected human DSCAM cDNA into mouse fibroblast L cells and analysed its expression. On Western blot analysis, antibodies raised against recombinant DSCAM-Ig3 recognized a 198 kDa protein band in the membrane fraction of DSCAM transfected L cells. Stable transformants expressing DSCAM showed uniform surface expression. DSCAM-expressing transfectants exhibited enhanced adhesive properties, aggregating with faster kinetics and forming aggregates in a homophilic manner. Divalent cations are not required for this cell aggregation. These results demonstrate that DSCAM is a cell adhesion molecule that can mediate cation-independent homophilic binding activity between DSCAM expressing cells. (C) 2000 Elsevier Science B.V. All rights reserved.