He John Cijiang, Neves Susana R, Jordan J Dedrick, Iyengar Ravi
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L levy Place, New York, NY 10029, USA.
Can J Physiol Pharmacol. 2006 Jul;84(7):687-94. doi: 10.1139/y06-025.
Neurite outgrowth is a complex differentiation process stimulated by many neuronal growth factors and transmitters and by electrical activity. Among these stimuli are ligands for G-protein-coupled receptors (GPCR) that function as neurotransmitters. The pathways involved in GPCR-triggered neurite outgrowth are not fully understood. Many of these receptors couple to Galphao, one of the most abundant proteins in the neuronal growth cones. We have studied the Go signaling network involved in neurite outgrowth in Neuro2A cells. Galphao can induce neurite outgrowth. The CB1 cannabinoid receptor, a Go/i-coupled receptor expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating Rap1, which promotes the Galphao-stimulated proteasomal degradation of Rap1GAPII. CB1-receptor-mediated Rap1 activation leads to the activation of a signaling network that includes the small guanosine triphosphate (GTP)ases Ral and Rac, the protein kinases Src, and c-Jun N-terminal kinase (JNK), which converge onto the activation of signal transducer and activator of transcription 3 (Stat3), a key transcription factor that mediates the gene expression process of neurite outgrowth in Neuro2A cells. This review describes current findings from our laboratory and also discusses alternative pathways that Go/i might mediate to trigger neurite outgrowth. We also analyze the role neurotransmitters, which stimulate Go/i to activate a complex signaling network controlling neurite outgrowth, play in regeneration after neuronal injury.
神经突生长是一个复杂的分化过程，受到多种神经元生长因子、递质以及电活动的刺激。这些刺激因素中包括作为神经递质发挥作用的G蛋白偶联受体（GPCR）的配体。GPCR触发神经突生长所涉及的信号通路尚未完全明确。许多这类受体与Gαo偶联，Gαo是神经元生长锥中最丰富的蛋白质之一。我们研究了Neuro2A细胞中参与神经突生长的Gαo信号网络。Gαo可诱导神经突生长。CB1大麻素受体是一种在Neuro2A细胞中内源性表达的与Gαo/i偶联的受体，它通过激活Rap1触发神经突生长，Rap1可促进Gαo刺激的Rap1GAPII蛋白酶体降解。CB1受体介导的Rap1激活导致一个信号网络的激活，该网络包括小GTP酶Ral和Rac、蛋白激酶Src以及c-Jun氨基末端激酶（JNK），这些信号汇聚到信号转导子和转录激活子3（Stat3）的激活上，Stat3是介导Neuro2A细胞中神经突生长基因表达过程的关键转录因子。这篇综述描述了我们实验室目前的研究发现，并讨论了Gαo/i可能介导触发神经突生长的其他途径。我们还分析了刺激Gαo/i激活控制神经突生长的复杂信号网络的神经递质在神经元损伤后再生中的作用。
