Role of the Go/i signaling network in the regulation of neurite outgrowth
Role of the Go/i signaling network in the regulation of neurite outgrowth
复制标题
DOI：
10.1139/y06-025
复制
发表时间：
2006-07-01
影响因子：
2.1
通讯作者：
Iyengar, Ravi
中科院分区：
文献类型：
--
作者：
He, John Cijiang;Neves, Susana R.;Iyengar, Ravi
神经突生长是一个复杂的分化过程，由许多神经元生长因子和递质以及电活动刺激。这些刺激物包括充当神经递质的 G 蛋白偶联受体 (GPCR) 的配体。 GPCR 触发的神经突生长所涉及的途径尚不完全清楚。许多受体与 G α(o) 偶联，G α(o) 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 G(o) 信号网络。 G alpha(o) 可以诱导神经突生长。 CB1 大麻素受体是 Neuro2A 细胞内源表达的 G(o/i) 偶联受体，通过激活 Rap1 触发神经突生长，从而促进 G α(o) 刺激的 Rap1GAPII 蛋白酶体降解。 CB1 受体介导的 Rap1 激活导致信号网络激活，其中包括小鸟苷三磷酸 (GTP) 酶 Ral 和 Rac、蛋白激酶 Src 和 c-Jun N 末端激酶 (JNK)，这些网络汇聚到信号转导器和转录激活剂 3 (Stat3) 的激活上，Stat3 是介导基因表达过程的关键转录因子。 Neuro2A 细胞中的神经突生长。这篇综述描述了我们实验室的最新发现，并讨论了 G(o/i) 可能介导的替代途径，以触发神经突生长。我们还分析了神经递质在神经元损伤后再生中的作用，神经递质刺激 G(o/i) 激活控制神经突生长的复杂信号网络。
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 G alpha(o), one of the most abundant proteins in the neuronal growth cones. We have studied the G(o) signaling network involved in neurite outgrowth in Neuro2A cells. G alpha(o) can induce neurite outgrowth. The CB1 cannabinoid receptor, a G(o/i)-coupled receptor expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating Rap1, which promotes the G alpha(o)-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 G(o/i) might mediate to trigger neurite outgrowth. We also analyze the role neurotransmitters, which stimulate G(o/i) to activate a complex signaling network controlling neurite outgrowth, play in regeneration after neuronal injury.