Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A.
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.
Deken
S L
SL
Department of Neurobiology, CIRC 446, University of Alabama at Birmingham, 1719 Sixth Avenue South, Birmingham, Alabama 35294-0021, USA.
Beckman
M L
ML
Boos
L
L
Quick
M W
MW
D000818:Animals; D000954:Antigens, Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001905:Botulinum Toxins / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D050485:GABA Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009865:Oocytes; D027361:Organic Anion Transporters; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013570:Synaptic Membranes / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D050827:Syntaxin 1; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D000954:Antigens, Surface; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C493415:Slc6a1 protein, rat; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D005680:gamma-Aminobutyric Acid; D001905:Botulinum Toxins