Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States.
Biochemistry. 2011 Aug 30;50(34):7295-310. doi: 10.1021/bi200405c. Epub 2011 Aug 5.
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, mono amine 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 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.
血浆膜和囊泡转运体对于生物胺，如多巴胺、去甲肾上腺素和 5-羟色胺，是一组在神经递质调节中起着关键作用的蛋白质。临床上，单胺转运体是许多用于治疗情绪障碍的治疗药物的主要作用靶点，也是高度成瘾性精神兴奋剂如可卡因、安非他命、甲基苯丙胺和 3,4-亚甲二氧基甲基苯丙胺的作用部位。在过去的十年中，使用酵母双杂交和蛋白质组学等方法已经鉴定出许多转运体相互作用蛋白，这表明这些转运体的功能和调节比以前预期的更为复杂。随着相互作用蛋白数量的增加，决定转运体合成、组装、靶向、运输和功能的规则开始被破译。尽管这些蛋白相互作用中的许多仍未被充分表征，但目前的知识开始揭示涉及单胺稳态、精神兴奋剂的分子作用以及潜在疾病机制的新型转运体机制。虽然需要进一步的研究来解析这些以及尚未确定的相互作用的时空分辨率，但认识到单胺转运体并非单独起作用，为大量可能的药理学干预开辟了道路。
