Living without DAT: Loss and compensation of the dopamine transporter gene in sauropsids (birds and reptiles).
Living without DAT: Loss and compensation of the dopamine transporter gene in sauropsids (birds and reptiles).
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DOI：
10.1038/srep14093
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发表时间：
2015-09-14
影响因子：
4.6
通讯作者：
Mello CV
中科院分区：
文献类型：
--
作者：
Lovell PV;Kasimi B;Carleton J;Velho TA;Mello CV
多巴胺转运体(DAT)是突触多巴胺(DA)可获得性的主要调节因子。它在运动控制、运动学习、记忆形成和寻求奖赏行为中起着关键作用，是可卡因和甲基苯丙胺的主要靶标，并被认为在脊椎动物中是保守的。然而，我们发现鸟类、鳄鱼和蜥蜴缺乏DAT基因。我们还发现，在多巴胺能细胞中，这一重要基因的史无前例的丢失被去甲肾上腺素转运体(NAT)基因而不是5-羟色胺转运体基因的表达所补偿，这解释了以前在鸟类纹状体中发现的DA再摄取活性的特殊药理学。这种意想不到的模式与祖先脊椎动物(例如鱼类)和哺乳动物的模式形成了鲜明对比，在哺乳动物中，NAT基因在去甲肾上腺素能细胞中选择性地表达。因此，鸟类/爬行动物和哺乳动物中的DA回路以不同基因施加的类似的再摄取机制工作，为多巴胺能细胞的基因表达调控以及奖赏和成瘾途径中关键分子的进化带来了新的见解。
The dopamine transporter (DAT) is a major regulator of synaptic dopamine (DA) availability. It plays key roles in motor control and motor learning, memory formation, and reward-seeking behavior, is a major target of cocaine and methamphetamines, and has been assumed to be conserved among vertebrates. We have found, however, that birds, crocodiles, and lizards lack the DAT gene. We also found that the unprecedented loss of this important gene is compensated for by the expression of the noradrenaline transporter (NAT) gene, and not the serotonin transporter genes, in dopaminergic cells, which explains the peculiar pharmacology of the DA reuptake activity previously noted in bird striatum. This unexpected pattern contrasts with that of ancestral vertebrates (e.g. fish) and mammals, where the NAT gene is selectively expressed in noradrenergic cells. DA circuits in birds/reptiles and mammals thus operate with an analogous reuptake mechanism exerted by different genes, bringing new insights into gene expression regulation in dopaminergic cells and the evolution of a key molecular player in reward and addiction pathways.