COBRE: LSU: PROJ 1:SYSTEM A TRANSPORTERS IN GLUTMATERGIC NEUROTRANSMISSION

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。 我们已经克隆并从功能上鉴定了编码蛋白SAT1和SAT2的cDNA，这两个蛋白是A系统中依赖Na+的中性氨基酸转运蛋白家族的第一个成员。A系统底物，如谷氨酰胺和丙氨酸，在许多细胞类型中的运输受到高度调控，因为这些氨基酸在神经传递、能量生成和氮代谢中发挥着重要作用。SAT1在突触传递中的识别。这些氨基酸在外周器官中的电摄取是由SAT2介导的，在神经元中，SAT2可能提供丙氨酸，作为α-酮戊二酸的氮供体，产生谷氨酸代谢池。由于谷氨酰胺是谷氨酸-谷氨酰胺循环中神经递质谷氨酸的关键前体，因此有理由提出检验这一假说，即这些转运体在调节大脑中主要兴奋性递质的合成中起关键作用。本研究的目的是研究谷氨酸能神经元在生理和病理生理条件下，在蛋白质合成水平和细胞间循环水平对这些基因的调控，并确定SAT1和SAT2是否是调节突触前谷氨酸合成和最终胞吐释放的潜在靶点。

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. We have cloned and functionally identified cDNAs encoding the proteins SAT1 and SAT2 that are the first members of the system A family of Na+-dependent neutral amino acid transporters. Transport of system A substrates, such as glutamine and alanine, in many cell types are highly regulated since these amino acids play important roles in neurotransmission, energy generation and in nitrogen metabolism. The identification of SAT1 in synaptic transmission. The electrogenic uptake of these amino acids in peripheral organs is mediated by SAT2, and in neurons, SAT2 may provide alanine, as a nitrogen donor to alpha-ketoglutarate, to generate a metabolic pool of glutamate. Since glutamine is a critical precursor for neurotransmitter glutamate via the glutamate-glutamine cycle, it is reasonable to propose to test the hypothesis that these transporters play key roles in regulating the synthesis of the major excitatory transmitter in the brain. The purpose of this proposal is to study the regulation of these genes in glutamatergic neurons at the level of protein synthesis, as well as at the level of cycling between cellular compartments, in response to physiological and pathophysiological conditions, and to determine whether SAT1 and SAT2 are potential targets to modulate presynaptic glutamate synthesis and eventual exocytotic release.