PNAS：酒精摄入有关的遗传变异
酗酒是非常普遍,但是很少是理解分子的原因。文章揭示在果蝇和人类中Ras抑制因子1(Rsu1)影响着乙醇消化。遗传因素在人类成瘾的发展发挥着重要作用。识别这些基因和理解他们的分子机制是必要的第一步发展的有针对性的治疗干预。文章中我们有从一个准确的遗传检查中单独分离来编码Ras抑制因子1(Rsu1)的基因，这基因能在果蝇,黑腹果蝇里改变对乙醇反应。
我们的行为、遗传和生化实验表明,在成年人中，从整合素细胞粘附分子发出信号给小GTPase Rac1调控成年人神经元的肌动蛋白动力和酒精消化偏好，Rsu1与这些都是相关的。我们还表明,变异在人类RSU1与改变饮酒和大脑活动奖励预测任务,从而验证我们方法的预测能力。
Rsu1在需要在成年人神经系统中存在以保持正常的敏感性，同时整合下游的素的细胞粘附分子和上游的Ras-related C3肉毒杆菌毒素衬底1(Rac1)GTPase调节肌动蛋白细胞骨架。乙醇偏好分析,全球Rsu1损失导致出现很天真的表现。相比之下,苍蝇缺乏Rsu1在大脑的蘑菇体只显示正常天真的表现,但却无法像正常的果蝇有乙醇偏好表现。
对来自超过2000人的数据的一项分析说，科研人员通过遗传筛查识别出了一种称为Ras抑制者1(Rsu1)的蛋白质，它参与了与果蝇的酒精偏好以及酒精敏感性有关的神经元信号传导，并且通过脑成像发现了Rsu1基因的变异不仅与人类青少年在预期获得奖赏时候的腹侧纹状体区域的激活有关，而且也与人类成年人和青少年的酒精摄入有关联。
原文链接：
Rsu1 regulates ethanol consumption in Drosophila and humans
原文摘要：
Alcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla.
doi:10.1073/PNAS.1417222112
作者：Shamsideen A. Ojelad
