Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.
Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.
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DOI：
10.1371/journal.pgen.1000898
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发表时间：
2010-04-08
期刊：
影响因子：
4.5
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Luo Y;Shan G;Guo W;Smrt RD;Johnson EB;Li X;Pfeiffer RL;Szulwach KE;Duan R;Barkho BZ;Li W;Liu C;Jin P;Zhao X
脆性X综合征（FXS）是遗传性智力低下最常见的一种形式，它是由功能性脆性X智力低下蛋白（FMRP）的缺失引起的。FMRP是一种rna结合蛋白，可以调节特定mrna的翻译。成人神经发生被认为是神经可塑性和记忆的重要过程，受多个分子水平的调控。在这项研究中，我们研究了Fmrp缺乏是否影响成人神经发生。我们表明，在脆性X综合征的小鼠模型中，成年神经发生确实发生了改变。Fmrp的缺失增加了成体神经祖细胞/干细胞（aNPCs）的增殖并改变了其命运规范。我们证明Fmrp调节aNPC功能的几个关键成分的蛋白表达，包括CDK4和GSK3β。GSK3β的失调导致Wnt信号通路活性降低，从而改变神经原素1的表达和aNPCs的命运规范。这些数据揭示了Fmrp在成人神经发生中的新调控作用和翻译调控。脆性X综合征是遗传性智力发育迟滞的最常见原因，其原因是功能性脆性X智力发育迟滞蛋白（FMRP）的缺失。FMRP是一种rna结合蛋白，已知可结合特定mrna并调节其在体内和体外的翻译。成人神经发生被认为是神经可塑性和记忆的重要过程，受多个分子水平的调控。本研究表明，Fmrp可以调节成体神经祖细胞/干细胞（aNPCs）的增殖和命运规范。这些数据揭示了Fmrp在成人神经发生中的一种新的调节作用。
Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis. Fragile X syndrome, the most common cause of inherited mental retardation, results from the loss of functional Fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein and is known to bind to specific mRNAs and to regulate their translation both in vitro and in vivo. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. Here we show that Fmrp could regulate the proliferation and fate specification of adult neural progenitor/stem cells (aNPCs). These data unveil a novel regulatory role for Fmrp in adult neurogenesis.
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影响因子：
2.5
作者：
Brennan, F. X.;Albeck, D. S.;Paylor, R.
通讯作者：
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