Nrg1/ErbB signaling networks in Schwann cell development and myelination.

Nrg1/ErbB signaling networks in Schwann cell development and myelination.
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DOI:
10.1016/j.semcdb.2010.08.008
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发表时间:
2010-12
影响因子:
7.3
通讯作者:
Birchmeier C
Birchmeier C
中科院分区:
生物学2区
文献类型:
--
作者:
Newbern J;Birchmeier C

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神经调节蛋白-1(Nrg1)通过与ErbB2/3受体结合,提供关键的轴突信号,调节雪旺细胞的增殖、迁移和髓鞘形成。对一些遗传模型的分析揭示了Nrg1/ErbB信号轴特异性的基本机制。Nrg1异构体的差异表达、Nrg1的加工以及ErbB受体的定位和运输是调控Nrg1/ErbB功能的重要调控主题。NRG1与ErbB2/3受体结合可激活细胞内信号转导通路,从而改变雪旺细胞的行为。在这里,我们回顾了定义了关键的Nrg1/ErbB信号组件,如Shp2,ERK1/2,FAK,rac1/CDC42和Calcineurin在体内雪旺细胞谱系发展中的作用的数据。这些调节器中的许多从Notch、整合素或G蛋白偶联受体提供的其他信号中接收汇聚信号。多种细胞外因子的信号转导可能作为关键的修饰物,使处于不同发育阶段的雪旺细胞以不同的方式对Nrg1/ErbB信号做出反应。
Neuregulin-1 (Nrg1) provides a key axonal signal that regulates Schwann cell proliferation, migration and myelination through binding to ErbB2/3 receptors. The analysis of a number of genetic models has unmasked fundamental mechanisms underlying the specificity of the Nrg1/ErbB signaling axis. Differential expression of Nrg1 isoforms, Nrg1 processing, and ErbB receptor localization and trafficking represent important regulatory themes in the control of Nrg1/ErbB function. Nrg1 binding to ErbB2/3 receptors results in the activation of intracellular signal transduction pathways that initiate changes in Schwann cell behavior. Here, we review data that has defined the role of key Nrg1/ErbB signaling components like Shp2, ERK1/2, FAK, Rac1/Cdc42 and calcineurin in development of the Schwann cell lineage in vivo. Many of these regulators receive converging signals from other cues that are provided by Notch, integrin or G-protein coupled receptors. Signaling by multiple extracellular factors may act as key modifiers and allow Schwann cells at different developmental stages to respond in distinct manners to the Nrg1/ErbB signal.
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