Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B.
Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B.
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DOI：
10.1523/jneurosci.1944-12.2012
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发表时间：
2012-12-05
期刊：
影响因子：
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通讯作者：
Rothenfluh A
中科院分区：
文献类型：
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作者：
Peru Y Colón de Portugal RL;Acevedo SF;Rodan AR;Chang LY;Eaton BA;Rothenfluh A
酒精使用障碍影响数百万人。然而，参与行为乙醇反应和成瘾的基因和信号通路知之甚少。在这里，我们确定了一个保守的生化途径，乙醇在果蝇的镇静作用的基础。Arf 6小GT3信号通路的突变导致对乙醇诱导的镇静的超敏反应。我们发现Arf 6在成人神经系统中起控制乙醇诱导行为的作用。我们还发现，果蝇Arfaptin蛋白直接结合到Arf 6和Rac 1 GTP酶的激活形式，Arfaptin的突变体也显示乙醇敏感性。Arf 6在Rac 1和Arfaptin的下游起作用，调节乙醇诱导的行为，因此我们证明了这种保守的Rac 1/Arfaptin/Arf 6通路是乙醇诱导的行为反应的主要介质。
Alcohol use disorders affect millions of individuals. However, the genes and signaling pathways involved in behavioral ethanol responses and addiction are poorly understood. Here we identify a conserved biochemical pathway that underlies the sedating effects of ethanol in Drosophila. Mutations in the Arf6 small GTPase signaling pathway cause hypersensitivity to ethanol-induced sedation. We show that Arf6 functions in the adult nervous system to control ethanol-induced behavior. We also find that the Drosophila Arfaptin protein directly binds to the activated forms of Arf6 and Rac1 GTPases, and mutants in Arfaptin also display ethanol-sensitivity. Arf6 acts downstream of Rac1 and Arfaptin to regulate ethanol-induced behaviors, and we thus demonstrate that this conserved Rac1/Arfaptin/Arf6 pathway is a major mediator of ethanol-induced behavioral responses.