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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。我们已经克隆和功能鉴定的cDNA编码的蛋白质SAT 1和SAT 2的系统A家族的Na+依赖的中性氨基酸转运蛋白的第一个成员。系统A底物如谷氨酰胺和丙氨酸在许多细胞类型中的转运受到高度调节，因为这些氨基酸在神经传递、能量产生和氮代谢中起重要作用。突触传递中SAT 1的鉴定。这些氨基酸在外周器官中的产电摄取由SAT 2介导，并且在神经元中，SAT 2可以提供丙氨酸作为α-酮戊二酸的氮供体，以产生谷氨酸的代谢池。由于谷氨酰胺是通过谷氨酸-谷氨酰胺循环的神经递质谷氨酸的关键前体，因此提出测试这些转运蛋白在调节脑中主要兴奋性递质的合成中起关键作用的假设是合理的。本提案的目的是研究这些基因在蛋白质合成水平的调节，以及在细胞室之间的循环水平，在生理和病理生理条件下，并确定是否SAT 1和SAT 2是潜在的目标，以调节突触前谷氨酸合成和最终胞吐释放。

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.