Serotonin Transporter Intracellular Structure Function Relationships

血清素转运体（SERT）在大脑中血清素的作用和循环中起着重要作用。SERT是一种质膜蛋白，它将5 -羟色胺结合在突触附近的细胞外空间，将其通过膜运输，并将其释放到细胞质中。它是摇头丸（3.4-亚甲基二氧甲基苯丙胺，MDMA）和可卡因等滥用药物以及抗抑郁药如百忧解和丙咪嗪等治疗药物的目标。它与多巴胺、去甲肾上腺素、GABA和甘氨酸等其他神经递质转运体密切相关。作为对SERT结构和功能更广泛的兴趣的一部分，很明显，转运体面向细胞质的部分

Serotonin transporter (SERT) plays an important role in the action and recycling of serotonin in the brain. SERT is a plasma membrane protein that binds serotonin in the extracellular space near a synapse, transports it across the membrane, and releases it to the cytoplasm. It is the target for drugs of abuse such as ecstasy (3.4-methylenedioxymethamphetamine, MDMA) and cocaine, as well as therapeutic drugs such as antidepressants like Prozac and imipramine. It is closely related to other neurotransmitter transporters such as those for dopamine, norepinephrine, GABA and glycine. As part of a wider interest in the structure and function of SERT, it has become apparent that the part of the transporter that faces the cytoplasm undergoes important conformational changes during transport. This intracellular domain consists of the NH2- and COOH-termini of the protein and five intracelluar loops. The current proposal seeks to understand the structure and function of these intracellular elements in three specific aims. The first of these is to scan the intracellular loops by cysteine mutagenesis to determine the boundaries between the loop and transmembrane domains. The second aim is to examine the possibility that intracellular loops interact specifically with each other to form the intracellular structure of the transporter. The third aim is to test the hypothesis that the translocation pathway for serotonin is formed, in part, by loops as well as transmembrane domains. It is expected that the results of these experiments will shed light on the structure and function of the related dopamine and norepinephrine transporters as well as of other members of the neurotransmitter transporter family.