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Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A

Nature Neuroscience volume 3, pages 998–1003 (2000)Cite this article

Abstract

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.

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Figure 1: GAT1 and syntaxin 1A physically and functionally interact in hippocampal neurons.
Figure 2: Residues 188–266 of syntaxin 1A mediate syntaxin 1A's association with GAT1.
Figure 3: The N-terminal cytoplasmic domain of GAT1 mediates the association with syntaxin 1A.
Figure 4: Syntaxin 1A increases plasma membrane GAT1 expression.
Figure 5: Syntaxin 1A inhibits GAT1 transport rates.
Figure 6: The N-terminal domain of GAT1 regulates transport rates.

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Acknowledgements

We thank K.L. Kirk and A.P. Naren for their assistance during the course of the study and S.A. Merritt for editorial suggestions. This work was supported in part by the W.M. Keck Foundation #931360 and National Institutes of Health grants DA10509, MH61468 to M.W.Q.

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  1. Department of Neurobiology, CIRC 446, University of Alabama at Birmingham, 1719 Sixth Avenue South, Birmingham, 35294-0021, Alabama, USA

    Scott L. Deken, Matthew L. Beckman, Laura Boos & Michael W. Quick

  2. Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, 35294-0021, Alabama, USA

    Matthew L. Beckman

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Correspondence to Michael W. Quick.

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Deken, S., Beckman, M., Boos, L. et al. Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A. Nat Neurosci 3, 998–1003 (2000). https://doi.org/10.1038/79939

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