Neurite outgrowth induced by cyclic AMP can be modulated by the α subunit of Go
Neurite outgrowth induced by cyclic AMP can be modulated by the α subunit of Go
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DOI：
10.1046/j.1471-4159.2000.0740151.x
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Suh-Kim, H
中科院分区：
文献类型：
--
作者：
Ghil, SH;Kim, BJ;Suh-Kim, H
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。在这里，我们报道 Go (oto) 的 a 亚基通过干扰环 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。 α o (α o(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αo(Q205L)失去了GTP酶活性，因此不能与Gβγ结合，给出了类似的结果，表明αo的作用不是通过Gβγ介导的。 (Q205L)的表达也抑制CREB激活。因此，Erk的αo(wt)或αo(Q205L)激活对于F11细胞中的神经元分化可能不是必需的，并且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 a subunit of Go (oto) 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 alpha o (alpha o(wt)) decreased the average length of neurites but increased the number of neurites per cell. An active mutant, alpha o(Q205L), which lost GTPase activity and thus could not bind to G beta gamma, gave similar results, suggesting that the effect of alpha o is not mediated through G beta gamma. Expression of (Q205L) also prohibited CREB activation. Thus, alpha o(wt) or alpha o(Q205L) activation of Erk may not be essential for neuronal differentiation in F11 cells and alpha o may cause changes in NOG by inhibiting CREB activation.