Doherty P, Williams E, Walsh F S
Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge, England.
Neuron. 1995 Jan;14(1):57-66. doi: 10.1016/0896-6273(95)90240-6.
Cerebellar neurons, cultured on monolayers of 3T3 fibroblasts or on a polylysine/extracellular matrix-coated substratum, responded to a soluble recombinant L1-Fc chimera by extending longer neurites than controls. The response was inhibited by pretreating neurons with antibodies to L1 or antibodies to the fibroblast growth factor (FGF) receptor. The response could also be inhibited by a range of pharmacological reagents that inhibit various steps in the signal transduction cascade which underlie a neurite outgrowth response to basic FGF. The response was of a similar magnitude and not additive with that induced by L1 expressed in a cellular substrate. These data show that L1 in neurons is capable of directing a neurite outgrowth response to a soluble L1-Fc chimera, and that neuronal FGF receptor function is required for this response. The data also show that the ability of cell adhesion molecules (CAMs) to stimulate neurite outgrowth can be dissociated from their ability to function as substrate-associated adhesion molecules and point to the potential of using CAM-Fc chimeras to promote nerve regeneration.
在3T3成纤维细胞单层或聚赖氨酸/细胞外基质包被的基质上培养的小脑神经元，对可溶性重组L1-Fc嵌合体的反应是，其神经突延伸得比对照更长。用抗L1抗体或抗成纤维细胞生长因子（FGF）受体抗体预处理神经元可抑制该反应。一系列抑制信号转导级联反应中不同步骤的药理试剂也可抑制该反应，这些步骤是对碱性FGF的神经突生长反应的基础。该反应的程度与细胞底物中表达的L1诱导的反应相似，且无叠加效应。这些数据表明，神经元中的L1能够引导对可溶性L1-Fc嵌合体的神经突生长反应，并且该反应需要神经元FGF受体功能。数据还表明，细胞粘附分子（CAMs）刺激神经突生长的能力可以与其作为底物相关粘附分子的功能分离，并指出使用CAM-Fc嵌合体促进神经再生的潜力。
