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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Erbin regulates NRG1 signaling and myelination
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Erbin regulates NRG1 signaling and myelination

机译：Erbin调节NRG1信号传导和髓鞘形成

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摘要

Neuregulin 1 (NRG1) plays a critical role in myelination. However, little is known about regulatory mechanisms of NRG1 signaling. We show here that Erbin, a protein that contains leucine-rich repeats (LRR) and a PSD95-Dlg-Zol (PDZ) domain and that interacts specifically with ErbB2, is necessary for NRG1 signaling and myelination of peripheral nervous system (PNS). In Erbin null mice, myelinated axons were hypomyelinated with reduced expression of P0, a marker of mature myelinating Schwann cells (SCs), whereas unmyelinated axons were aberrantly ensheathed in Remak bundles, with increased numbers of axons in the bundles and in pockets. The morphological deficits were associated with decreased nerve conduction velocity and increased sensory threshold to mechanistic stimulation. These phenotypes were duplicated in erbin~(ΔC/ΔC) mice, in which Erbin lost the PDZ domain to interact with ErbB2. Moreover, ErbB2 was reduced at protein levels in both Erbin mutant sciatic nerves, and ErbB2 became unstable and NRG1 signaling compromised when Erbin expression was suppressed. These observations indicate a critical role of Erbin in myelination and identify a regulatory mechanism of NRG1 signaling. Our results suggest that Erbin, via the PDZ domain, binds to and stabilizes ErbB2, which is necessary for NRG1 signaling that has been implicated in tumorigenesis, heart development, and neural function.
机译：神经调节蛋白1（NRG1）在髓鞘形成中起关键作用。但是，关于NRG1信号的调控机制知之甚少。我们在这里显示，Erbin，一种蛋白质，含有丰富的亮氨酸重复序列（LRR）和PSD95-Dlg-Zol（PDZ）域，并且与ErbB2特异性相互作用，对于NRG1信号传导和周围神经系统的髓鞘化是必需的。在Erbin无效的小鼠中，髓鞘轴突的髓鞘过少，P0的表达降低，P0是成熟的髓鞘雪旺细胞（SCs）的标志物，而未髓鞘的轴突则被异常包裹在Remak束中，束丛和口袋中的轴突数量增加。形态缺陷与神经传导速度降低和机械刺激的感觉阈值升高有关。这些表型在erbin〜（ΔC/ΔC）小鼠中重复出现，其中Erbin失去了PDZ结构域以与ErbB2相互作用。此外，在Erbin突变坐骨神经中，ErbB2的蛋白水平均降低，当Erbin表达受到抑制时，ErbB2变得不稳定，NRG1信号受损。这些观察结果表明埃尔宾在髓鞘形成中的关键作用，并确定了NRG1信号传导的调节机制。我们的研究结果表明，Erbin通过PDZ域与ErbB2结合并使其稳定，这对于涉及肿瘤发生，心脏发育和神经功能的NRG1信号传导是必需的。

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    Yanmei Tao; Penggao Dai; Yu Liu; Sylvie Marchetto; Wen-Cheng Xiong; Jean-Paul Borg; Lin Mei;

  • 作者单位

    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912;

    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912;

    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912;

    lnstitut National de la Sante et de la Recherche Medicale, U891, Centre de Recherche en Cancerologie de Marseille, Pharmacologie Moleculaire, Marseille, F-13009 France lnstitut Paoli-Calmettes, Marseille, F-13009 France Faculty of Pharmacy, Universite de la Mediterranee, F-13007, Marseille, France;

    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912;

    lnstitut National de la Sante et de la Recherche Medicale, U891, Centre de Recherche en Cancerologie de Marseille, Pharmacologie Moleculaire, Marseille, F-13009 France lnstitut Paoli-Calmettes, Marseille, F-13009 France Faculty of Pharmacy, Universite de la Mediterranee, F-13007, Marseille, France;

    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    ErbB2; PDZ; protein stability; schwann cells; akt;

    机译：ErbB2;PDZ;蛋白质稳定性;雪旺细胞;Akt;

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