Matrin-3 is essential for fibroblast growth factor 2-dependent maintenance of neural stem cells.

Matrin-3 is essential for fibroblast growth factor 2-dependent maintenance of neural stem cells.
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DOI:
10.1038/s41598-018-31597-x
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发表时间:
2018-09-07
期刊:
影响因子:
4.6
通讯作者:
Niimori D
Niimori D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Niimori-Kita K;Tamamaki N;Koizumi D;Niimori D

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为了研究神经干细胞维持的机制,我们进行了针对核磷酸化蛋白的二维荧光差示凝胶电泳法(2D-DGE)。在成纤维细胞生长因子2(FGF2)刺激下,神经干细胞(NSCs)中检测到核磷酸化蛋白Matrin-3。Matrin-3在小鼠胚胎脑室下区和脑室区有表达。小干扰RNA(SiRNA)介导的Matrin-3基因敲除可在体外诱导NSCs向神经元分化,并在体内改变胎脑的脑层结构。将丝氨酸208位点突变为丙氨酸的Matrin-3质粒(Ser208Ala突变体Matrin3)和抑制可磷酸化Matrin-3 Ser208残基的毛细血管扩张共济失调突变激酶(ATM Kinase),可诱导神经元分化,并抑制神经球形成干细胞的增殖。因此,我们的蛋白质组学方法表明,Matrin-3的磷酸化对于体外和体内依赖FGF2的神经干细胞的维持是必不可少的。
To investigate the mechanisms underlying the maintenance of neural stem cells, we performed two-dimensional fluorescence-difference gel electrophoresis (2D-DIGE) targeting the nuclear phosphorylated proteins. Nuclear phosphorylated protein Matrin-3 was identified in neural stem cells (NSCs) after stimulation using fibroblast growth factor 2 (FGF2). Matrin-3 was expressed in the mouse embryonic subventricular and ventricular zones. Small interfering RNA (siRNA)-mediated knockdown of Matrin-3 caused neuronal differentiation of NSCs in vitro, and altered the cerebral layer structure of foetal brain in vivo. Transfection of Matrin-3 plasmids in which the serine 208 residue was point-mutated to alanine (Ser208Ala mutant Matrin3) and inhibition of Ataxia telangiectasia mutated kinase (ATM kinase), which phosphorylates Matrin-3 Ser208 residue, caused neuronal differentiation and decreased the proliferation of neurosphere-forming stem cells. Thus, our proteomic approach revealed that Matrin-3 phosphorylation was essential for FGF2-dependent maintenance of NSCs in vitro and in vivo.
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