Proteins Interacting with Monoamine Transporters: Current State and Future Challenges
Proteins Interacting with Monoamine Transporters: Current State and Future Challenges
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DOI：
10.1021/bi200405c
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发表时间：
2011-08-30
期刊：
影响因子：
2.9
通讯作者：
Torres, Gonzalo E.
中科院分区：
文献类型：
--
作者：
Sager, Jonathan J.;Torres, Gonzalo E.
生物胺、多巴胺、去甲肾上腺素和5-羟色胺的质膜和囊泡转运蛋白代表了一组在神经传递调节中起关键作用的蛋白质。在临床上，单胺转运蛋白是用于治疗情绪障碍的许多治疗剂的作用的主要靶标，以及高度成瘾性精神兴奋剂如可卡因、安非他明、甲基安非他明和3，4-亚甲基二氧基甲基安非他明的作用位点。在过去的十年中，使用诸如酵母双杂交和蛋白质组学的方法已经鉴定了大量转运蛋白相互作用蛋白，这表明这些转运蛋白的功能和调节比以前预期的更复杂。随着相互作用蛋白质数量的增加，转运蛋白合成、组装、靶向、运输和功能的规则开始被破译。虽然许多这些蛋白质的相互作用还没有得到充分的表征，目前的知识开始阐明新的转运机制参与单胺稳态，精神兴奋剂的分子作用，和潜在的疾病机制。虽然未来的研究解决这些，但未知的，相互作用的空间和时间分辨率将是必要的，单胺转运蛋白不单独工作的实现开辟了途径，可能的药理学干预过多。
Plasma membrane and vesicular transporters for the biogenic amines, dopamine, norepinephrine, and serotonin, represent a group of proteins that play a crucial role in the regulation of neurotransmission. Clinically, monoamine transporters are the primary targets for the actions of many therapeutic agents used to treat mood disorders, as well as the site of action for highly addictive psychostimulants such as cocaine, amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine, Over the past decade, the use of approaches such as yeast two-hybrid and proteomics has identified a multitude of transporter interacting proteins, suggesting that the function and regulation of these transporters are more complex than previously anticipated. With the increasing number of interacting proteins, the rules dictating transporter synthesis, assembly, targeting, trafficking, and function are beginning to on be deciphered. Although many of these protein interactions have yet to be fully characterized, current knowledge is beginning to shed light on novel transporter mechanisms involved in monoamine homeostasis, the molecular actions of psychostimulants, and potential disease mechanisms. While future studies resolving the spatial and temporal resolution of these, and yet unknown, interactions will be needed, the realization that monoamine transporters do not work alone opens the path to a plethora of possible pharmacological interventions.