STRUCTURAL & FUNCTIONAL STUDIES OF HUMAN VESICULAR NEUROTRANSMITTER TRANSPORTERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 神经递质的跨膜运输对于神经元之间的正确信号传递是至关重要的。运输过程是由不同类别的膜运输蛋白介导的，这些膜运输蛋白在控制突触间隙中的神经递质浓度方面起着关键作用。总体而言，这些转运体可分为细胞内囊泡转运体和质膜转运体，前者负责将胞浆中的递质隔离到突触小泡中，后者负责将释放的递质从细胞外空间隔离。细胞内转运蛋白分为三类：囊泡胺转运蛋白(SLC18)、囊泡抑制性氨基酸转运蛋白家族(SLC32)和囊泡谷氨酸转运蛋白(SLC17)。质膜转运蛋白分为两大类：高亲和力谷氨酸转运蛋白和钠氯偶联转运蛋白。后者是最大的一类，包括多巴胺、去甲肾上腺素、甘氨酸和GABA的转运体。 主要的研究目的是通过利用结构数据来进行功能研究，以提高我们对人类囊泡神经递质转运体的理解。然后，同源建模可以用于为同一家族的蛋白质产生高质量的结构模型，使我们能够计划对每个成员进行特定的功能研究，并可能使设计符合特定靶点的小分子成为可能(药物设计)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The transmembrane transport of neurotransmitters is of fundamental importance for proper signaling between neurons. The transport processes are mediated by distinct classes of membrane transport proteins that have key roles in controlling the neurotransmitter concentration in the synaptic cleft. Overall, these transporters can be classed as intracellular vesicular transporters that are responsible for sequestering transmitters from the cytoplasm into synaptic vesicles, and plasma membrane transporters that are responsible for sequestering released transmitter from the extracellular space. There are three subclasses of intracellular transporters: the vesicular amine transporters (SLC18), the vesicular inhibitory amino acid transporter family (SLC32) and the vesicular glutamate transporters (SLC17). There are two major subclasses of plasma membrane transporter: the high-affinity glutamate transporters and the Na+Cl -coupled transporters. The latter subclass is the largest and includes transporters of dopamine, norepinephrine, glycine and GABA. The main research objective is to improve our understanding of the human vesicular neurotransmitter transporters, by utilizing structural data to perform functional studies. Homology modeling could then be used to produce high-quality structural models for proteins from the same family, allowing us to plan specific functional studies on each member, and possibly enabling the design of small molecules that fit the specific targets (drug design).