Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells
Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells
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DOI：
10.1016/j.brainres.2014.11.041
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发表时间：
2015-01-30
期刊：
影响因子：
2.9
通讯作者：
Mutoh, Tatsuro
中科院分区：
文献类型：
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作者：
Fukuda, Yu;Fukui, Takao;Mutoh, Tatsuro
高亲和力神经生长因子受体Trk的激活通过多个过程发生，包括质膜脂筏内的移位和聚集、二聚化和自磷酸化。在这里，我们发现感染痘苗病毒的炎症兔皮肤的非蛋白质提取物(Neurotroin(R))提高了NGF信号转导的效率。在过度表达Trk的大鼠嗜铬细胞瘤PC12细胞(PCtrk细胞)中，Neurotroin以一种依赖于Trk激酶活性的方式增强在次适浓度的NGF(2 ng/mL)下观察到的不足的轴突生长。细胞暴露于神经妥乐平可导致Trk-GM1复合体的积聚，但不影响Trk的二聚化或磷酸化状态。神经生长因子刺激后，神经妥乐平显著促进了神经生长因子诱导的Trk自磷酸化的时间进程。这些观察提供了一种控制NGF信号效率的独特机制，并提高了Neurotroin对与神经营养素功能障碍相关的各种神经疾病的治疗潜力。(C)2014爱思唯尔B.V.保留所有权利。
Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin (R)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2 ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction. (C) 2014 Elsevier B.V. All rights reserved.