Molecular Networks of DYX1C1 Gene Show Connection to Neuronal Migration Genes and Cytoskeletal Proteins

Molecular Networks of DYX1C1 Gene Show Connection to Neuronal Migration Genes and Cytoskeletal Proteins
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DOI:
10.1016/j.biopsych.2012.08.012
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发表时间:
2013-03-15
影响因子:
10.6
通讯作者:
Tapia-Paez, Isabel
Tapia-Paez, Isabel
中科院分区:
医学1区
文献类型:
--
作者:
Tammimies, Kristiina;Vitezic, Morana;Tapia-Paez, Isabel

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背景资料:阅读障碍易感性1候选基因1(DYX1C1)最近已与阅读障碍和阅读分数在几个人口样本。DYX1C1还被证明影响神经元迁移和调节雌激素受体信号转导.方法:我们通过基因表达和蛋白质相互作用分析DYX1C1在人神经母细胞瘤细胞系中的分子网络.结果:我们发现DYX1C1可以调节神经系统发育和神经元迁移基因的表达,如JNK,并与许多细胞骨架蛋白相关。我们还表明,活细胞成像DYX1C1调节依赖于其tetratricopeptide重复和DYX1蛋白结构域的人神经母细胞瘤细胞系的细胞迁移。DYX1结构域是一个新的高度保守的结构域,在这项研究中确定的DYX1C1蛋白回收从广泛的真核生物species.Conclusions的多序列比对:我们的研究结果有助于假设,阅读障碍有一个发育神经生物学的基础上连接DYX1C1与许多基因参与神经元迁移disorders。
Background: The dyslexia susceptibility 1 candidate 1 (DYX1C1) gene has recently been associated with dyslexia and reading scores in several population samples. The DYX1C1 has also been shown to affect neuronal migration and modulate estrogen receptor signaling.Methods: We have analyzed the molecular networks of DYX1C1 by gene expression and protein interaction profiling in a human neuroblastoma cell line.Results: We find that DYX1C1 can modulate the expression of nervous system development and neuronal migration genes such as RELN and associate with a number of cytoskeletal proteins. We also show by live cell imaging that DYX1C1 regulates cell migration of the human neuroblastoma cell line dependent on its tetratricopeptide repeat and DYX1 protein domains. The DYX1 domain is a novel highly conserved domain identified in this study by multiple sequence alignment of DYX1C1 proteins recovered from a wide range of eukaryotic species.Conclusions: Our results contribute to the hypothesis that dyslexia has a developmental neurobiological basis by linking DYX1C1 with many genes involved in neuronal migration disorders.