Back signaling by the Nrg-1 intracellular domain.

Back signaling by the Nrg-1 intracellular domain.
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DOI:
10.1083/jcb.200212085
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发表时间:
2003-06-23
影响因子:
7.8
通讯作者:
Talmage, DA
Talmage, DA
中科院分区:
生物学1区
文献类型:
--
作者:
Bao, JX;Wolpowitz, D;Role, LW;Talmage, DA

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神经调节蛋白-1(Nrg-1)是erbB受体的配体,其跨膜异构体包括具有EGF样序列的胞外结构域和功能未知的高度保守的胞内结构域(ICD)。在本文中,我们证明了跨膜异构体的NRG-1是神经元中的双向信号分子。Nrg-1反向信号传导的刺激包括erbB受体二聚体与Nrg-1胞外结构域的结合和神经元去极化。这些刺激引起Nrg-1的蛋白水解释放和ICD易位到细胞核。一旦在细胞核中,Nrg-1 ICD抑制几种细胞凋亡调节因子的表达,导致体外神经元细胞死亡减少。因此,受调节的Nrg-1蛋白水解加工导致似乎介导Nrg-1表达神经元的接触和活性依赖性存活的逆行信号传导。
Transmembrane isoforms of neuregulin-1 (Nrg-1), ligands for erbB receptors, include an extracellular domain with an EGF-like sequence and a highly conserved intracellular domain (ICD) of unknown function. In this paper, we demonstrate that transmembrane isoforms of Nrg-1 are bidirectional signaling molecules in neurons. The stimuli for Nrg-1 back signaling include binding of erbB receptor dimers to the extracellular domain of Nrg-1 and neuronal depolarization. These stimuli elicit proteolytic release and translocation of the ICD of Nrg-1 to the nucleus. Once in the nucleus, the Nrg-1 ICD represses expression of several regulators of apoptosis, resulting in decreased neuronal cell death in vitro. Thus, regulated proteolytic processing of Nrg-1 results in retrograde signaling that appears to mediate contact and activity-dependent survival of Nrg-1–expressing neurons.
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