Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell adhesion molecule that mediates homophilic intercellular adhesion

Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell adhesion molecule that mediates homophilic intercellular adhesion
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DOI:
10.1006/bbrc.2001.5214
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发表时间:
2001-07-20
影响因子:
3.1
通讯作者:
Yamakawa, K
Yamakawa, K
中科院分区:
生物学4区
文献类型:
--
作者:
Agarwala, KL;Ganesh, S;Yamakawa, K

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DSCAM是参与神经元分化的保守基因,是细胞粘附分子Ig超家族的成员。在此,我们报告了位于染色体11q23上的人类DSCAM(唐氏综合征细胞粘附分子)旁对话体DSCAML1的功能特征。推导出的DSCAML1蛋白含有10个Ig结构域、6个纤维连接蛋白- iii结构域和1个胞内结构域,它们在结构上都与DSCAM相同。与DSCAM相比,DSCAML1蛋白与胞外结构域的同源性为64%,与胞质结构域的同源性为45%。在小鼠大脑中,DSCAML1主要在小脑浦肯野细胞、齿状回颗粒细胞以及大脑皮层和嗅球的神经元中表达。生化和免疫荧光分析表明,DSCAML1是一种靶向分化PC12细胞轴突特征的细胞表面分子。DSCAML1表现出不需要二价阳离子的亲同型结合活性。基于其结构和功能特性以及与DSCAM的相似性,我们认为DSCAML1可能参与神经网络的形成和维持。DSCAML1的染色体位点使其成为11q23上定位的神经疾病(如吉尔斯·德·拉·图雷特和雅各布森综合征)的理想候选者。(C) 2001学术出版社。
DSCAM a conserved gene involved in neuronal differentiation, is a member of the Ig superfamily of cell adhesion molecules. Herein, we report the functional characterization of a human DSCAM (Down syndrome cell adhesion molecule) paralogue, DSCAML1, located on chromosome 11q23. The deduced DSCAML1 protein contains 10 Ig domains, six fibronectin-III domains, and an intracellular domain, all of which are structurally identical to DSCAM. When compared to DSCAM, DSCAML1 protein showed 64% identity to the extracellular domain and 45% identity to the cytoplasmic domain. In the mouse brain, DSCAML1 is predominantly expressed in Purkinje cells of the cerebellum, granule cells of the dentate gyrus, and in neurons of the cerebral cortex and olfactory bulb. Biochemical and immunofluorescence analyses indicated that DSCAML1 is a cell surface molecule that targets axonal features in differentiated PC12 cells. DSCAML1 exhibits homophilic binding activity that does not require divalent cations. Based on its structural and functional properties and similarities to DSCAM we suggest that DSCAML1 may be involved in formation and maintenance of neural networks. The chromosomal locus for DSCAML1 makes it an ideal candidate for neuronal disorders (such as Gilles de la Tourette and Jacobsen syndromes) that have been mapped on 11q23. (C) 2001 Academic Press.