Suppression of neurite outgrowth by high-dose nerve growth factor is independent of functional p75NTR receptors
Suppression of neurite outgrowth by high-dose nerve growth factor is independent of functional p75NTR receptors
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DOI：
10.1016/j.nbd.2003.09.009
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发表时间：
2004-02-01
影响因子：
6.1
通讯作者：
Windebank, AJ
中科院分区：
文献类型：
--
作者：
Conti, AM;Brimijoin, S;Windebank, AJ
我们之前已经证明，高浓度的神经生长因子可以抑制感觉神经元的神经突生长。抑制作用可由 p75NTR 或 TrkA 受体介导。我们在大鼠背根神经节神经元和 p75NTR 敲除小鼠的背根神经节培养物中使用了 REX 抗体对 p75NTR 的功能性阻断。在这两个系统中，高剂量 NGF 抑制神经突生长，这意味着 p75NTR 不参与神经突生长的抑制。暴露于荧光标记 NGF 的分离背根神经节神经元的共焦图像显示配体内化。放射性配体结合表明用 200 ng/ml NGF 处理 1 小时后，背根神经节表面的高亲和力结合位点消失。下游信号传导显示 MAPK (Erk(1-2)) 持续过度磷酸化，但 SNT 或 Akt 则不然。高剂量 NGF 可能独立于 p75NTR 诱导受体 TrkA 的细胞质重新定位和轴突生长停滞。 (C) 2003 Elsevier Inc. 保留所有权利。
We have previously demonstrated that high concentrations of nerve growth factor suppress neurite outgrowth from sensory neurons. Inhibition could be mediated by either the p75NTR or TrkA receptor. We used a functional block of p75NTR by REX antibody in rat dorsal root ganglion neurons and dorsal root ganglion cultures from p75NTR knockout mice. In both systems, high-dose NGF inhibited neurite outgrowth, implying that p75NTR is not involved in suppression of neurite outgrowth. Confocal images of dissociated dorsal root ganglion neurons exposed to fluorescence-tagged NGF showed ligand internalization. Radioligand binding indicated disappearance of high-affinity binding sites from the surface of dorsal root ganglia after treatment with 200 ng/ml NGF for 1 h. Downstream signaling showed sustained hyperphosphorylation of MAPK (Erk(1-2)) but not of SNT or Akt. Highdose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR. (C) 2003 Elsevier Inc. All rights reserved.