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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Surface / drug effects
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Antigens, Surface / genetics
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Antigens, Surface / metabolism*
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Botulinum Toxins / pharmacology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Cricetinae
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GABA Plasma Membrane Transport Proteins
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Hippocampus / cytology
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Hippocampus / metabolism
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Membrane Transport Proteins*
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology
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Neurons / metabolism
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Oocytes
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Organic Anion Transporters*
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Protein Structure, Tertiary / physiology
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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RNA, Messenger / pharmacology
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Rats
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Synaptic Membranes / metabolism*
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Synaptic Transmission / physiology*
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Synaptic Vesicles / metabolism
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Syntaxin 1
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Xenopus
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gamma-Aminobutyric Acid / metabolism*
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gamma-Aminobutyric Acid / pharmacology
Substances
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Antigens, Surface
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Carrier Proteins
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GABA Plasma Membrane Transport Proteins
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Membrane Proteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Organic Anion Transporters
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RNA, Messenger
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Slc6a1 protein, rat
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Stx1a protein, rat
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Syntaxin 1
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gamma-Aminobutyric Acid
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Botulinum Toxins