Neural adhesion molecules L1 and CHL1 are survival factors for motoneurons
Neural adhesion molecules L1 and CHL1 are survival factors for motoneurons
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DOI：
10.1002/jnr.20517
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发表时间：
2005-06-01
影响因子：
4.2
通讯作者：
Henderson, CE
中科院分区：
文献类型：
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作者：
Nishimune, H;Bernreuther, C;Henderson, CE
许多对体内运动神经元具有存活活性的神经营养因子首次通过纯化的胚胎运动神经元培养被鉴定出来。L1神经细胞黏附分子在大脑发育中有多种作用。原位杂交和RT-PCR结果表明，L1mRNA在胚胎和出生后脊髓运动神经元中均有显著表达。因此，我们在没有营养因子但含有L1-Fc和CHL1-Fc融合蛋白的情况下，从E14大鼠胚胎中培养出纯化的运动神经元。L1-FC以剂量依赖的方式(EC50=10 pm)阻止了BDNF挽救的大约一半运动神经元的死亡，CHL1-FC挽救了与L1-FC相同数量的运动神经元，而P0-FC在相同浓度下几乎没有神经营养活性。LY294002和PD98059完全抑制了L1和CHL1诱导的存活，表明MEK和PI3K信号通路都是这些分子信号转导所必需的。L1可以通过成纤维细胞生长因子受体FGFR1在其他类型的细胞中发出信号。在运动神经元培养中，亚适浓度的L1和亚适浓度的成纤维细胞生长因子-2的作用是相加的，但在L1-Fc的存在下，最佳浓度的成纤维细胞生长因子-2(50 ng/ml)的作用不会进一步增强。因此，在该系统中，FDF和L1也可以使用相似的信令路径。(C)2005年Wiley-Liss，Inc.
Many neurotrophic factors with survival activity for motoneurons in vivo were first identified using cultures of purified embryonic motoneurons. The L1 neural cell adhesion molecule has multiple roles in brain development. We showed by in situ hybridization and RT-PCR that L1 mRNA was expressed at significant levels in motoneurons of embryonic and postnatal spinal cord. We therefore cultured purified motoneurons from E14 rat embryos in the absence of trophic factors but with L1-Fc and CHL1-Fc fusion proteins. L1-Fc prevented the death of approximately half of the motoneurons that were saved by BDNF in a dose-dependent manner (EC50 = 10 pM)- CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations. Survival induced by L1 and CHL1 was completely inhibited by 20 mu M LY294002 and PD98059, indicating that both MEK and PI3K pathways are required for signaling by these molecules. L1 can signal in other cell types through the FGF receptor FGFR1. In cultures of motoneurons, effects of suboptimal concentrations of L1 and suboptimal concentrations of FGF-2 were additive, but the effects of optimal concentrations of FGF-2 (50 ng/ml) were not further increased in the presence of L1-Fc. Thus, in this system, too, FdF and L1 may use similar signaling pathways. (c) 2005 Wiley-Liss, Inc.