Neurite outgrowth induced by cyclic AMP can be modulated by the alpha subunit of Go.
Neurite outgrowth induced by cyclic AMP can be modulated by the alpha subunit of Go.
复制标题
环 AMP 诱导的神经突生长可以通过 Go 的 α 亚基调节。
作者：
S. Ghil;B. Kim;Y. Lee;H. Suh
尽管在神经组织中发现了大量的Go，并且它与神经元分化有关，但Go如何调节神经元分化的机制尚未明确。在此，我们报道 Go 的 α 亚基 (alphao) 通过干扰环 AMP (cAMP) 启动的信号通路来调节神经突生长。在 F11 细胞中，cAMP 诱导神经突生长并激活 cAMP 反应元件结合蛋白 (CREB)。特异性抑制 cAMP 依赖性蛋白激酶可降低 CREB 活性和神经突生长 (NOG)。有趣的是，cAMP 降低了细胞外信号调节激酶 (Erk) 的磷酸化。 Ras 的显性失活形式和活性形式都不会改变神经突的生长。 αo (alphao(wt)) 的表达减少了神经突的平均长度，但增加了每个细胞的神经突数量。活性突变体 alphaoQ205L 失去了 GTPase 活性，因此无法与 Gbetagamma 结合，也得到了类似的结果，表明 alphao 的作用不是通过 Gbetagamma 介导的。 ao(wt) 或 alphaoQ205L 的表达也抑制 CREB 激活。因此，Erk 的激活对于 F11 细胞的神经元分化可能不是必需的，αo 可能通过抑制 CREB 激活而引起 NOG 的变化。
Although abundant Go has been found in nervous tissues and it has been implicated in neuronal differentiation, the mechanism of how Go modulates neuronal differentiation has not been defined. Here, we report that the alpha subunit of Go (alphao) modulates neurite outgrowth by interfering with the signaling pathway initiated by cyclic AMP (cAMP). In F11 cells, cAMP induced neurite outgrowth and activated cAMP-responsive element binding protein (CREB). Specific inhibition of cAMP-dependent protein kinase reduced both CREB activity and neurite outgrowth (NOG). Interestingly, cAMP reduced phosphorylation of extracellular signal-regulated kinase (Erk). Neither a dominant negative form nor an active form of Ras altered neurite outgrowth. Expression of alphao (alphao(wt)) decreased the average length of neurites but increased the number of neurites per cell. An active mutant, alphaoQ205L, which lost GTPase activity and thus could not bind to Gbetagamma, gave similar results, suggesting that the effect of alphao is not mediated through Gbetagamma. Expression of ao(wt) or alphaoQ205L also prohibited CREB activation. Thus, activation of Erk may not be essential for neuronal differentiation in F11 cells and alphao may cause changes in NOG by inhibiting CREB activation.