Deken S L, Beckman M L, Boos L, Quick M W
Department of Neurobiology, CIRC 446, University of Alabama at Birmingham, 1719 Sixth Avenue South, Birmingham, Alabama 35294-0021, USA.
Nat Neurosci. 2000 Oct;3(10):998-1003. doi: 10.1038/79939.
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.
质膜γ-氨基丁酸（GABA）转运体通过神经递质的再摄取参与神经信号传导。介导GABA转运和调节转运的转运体结构域尚未完全清楚。在本实验中，GABA转运体GAT1的N端胞质结构域调节底物转运速率。该结构域直接与 syntaxin 1A相互作用，syntaxin 1A是一种参与神经递质释放、钙通道调节和囊性纤维化跨膜调节因子（CFTR）氯通道调节的可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白。这种相互作用导致转运体转运速率降低。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转运，并确定了参与递质释放和再摄取的机制之间的直接联系。
