Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A
Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A
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DOI：
10.1038/79939
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发表时间：
2000-10-01
影响因子：
25
通讯作者：
Quick, MW
中科院分区：
文献类型：
--
作者：
Deken, SL;Beckman, ML;Quick, MW
质膜 GABA 转运蛋白通过重新摄取神经递质参与神经信号传导。介导 GABA 易位和调节运输的转运蛋白的域尚不清楚。在本实验中，GABA 转运蛋白 GAT1 的 N 端胞质结构域调节底物转运速率。该结构域直接与突触蛋白 1A 相互作用，突触蛋白 1A 是一种 SNARE 蛋白，参与神经递质释放以及钙通道和囊性纤维化跨膜调节器 (CFTR) 氯离子通道的调节。这种相互作用导致转运蛋白转运速率降低。这些数据表明，GABA 的细胞内结构域和蛋白质-蛋白质相互作用调节底物易位，并确定参与递质释放和再摄取的机制之间的直接联系。
Plasma membrane GABA transporters participate in neural signaling through re-uptake of neurotransmitter. The domains of the transporter that mediate GABA translocation and regulate transport are not well understood. In the present experiments, the N-terminal cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates. This domain directly interacted with syntaxin 1A, a SNARE protein involved in both neurotransmitter release and modulation of calcium channels and cystic fibrosis transmembrane regulator (CFTR) chloride channels. The interaction resulted in a decrease in transporter transport rates. These data demonstrate that intracellular domains of the GABA and protein-protein interactions regulate substrate translocation, and identify a direct link between the machinery involved in transmitter release and re-uptake.