Syntaxin 1A up-regulates GABA transporter expression by subcellular redistribution.
Neurotransmitter transporters are regulated through a variety of signal transduction mechanisms which appear to operate in order to maintain appropriate levels of transmitter in the synaptic cleft. One such mechanism is the trafficking of the transporter in association with synaptic vesicle release machinery. This report examines the specifics of trafficking regulation of the rat brain GABA transporter GAT1 by syntaxin 1A, a plasma membrane component of the SNARE complex which is involved in vesicle membrane fusion. In hippocampal neurons, botulinum neurotoxin 1C, which specifically cleaves syntaxin 1A, down-regulates plasma membrane GAT1 levels as assessed by surface biotinylation, suggesting that syntaxin 1A is a positive regulator of GAT1 surface expression. The up-regulation correlates with a decrease in intracellular GAT1 levels and is complete within several minutes. These data suggest that syntaxin 1A mediates the redistribution of GAT1 on a time scale important for the rapid regulation of extracellular GABA levels. Expression of different syntaxin 1A constructs in Xenopus oocytes suggests that several portions of the syntaxin 1A molecule are required for the trafficking of GAT1. These data suggest that the trafficking of GAT1 will be subject to regulatory control by the many molecules known to interact with various domains of syntaxin 1A.
Horton
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Department of Neurobiology, University of Alabama at Birmingham, 35294-0021, USA.
Quick
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MW
D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000378:metabolism*; D019921:Biotinylation; D001905:Botulinum Toxins / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D050600:SNARE Proteins; D015398:Signal Transduction; D050827:Syntaxin 1; D013997:Time Factors; D015854:Up-Regulation; D033921:Vesicular Transport Proteins; D014981:Xenopus / Q000378:metabolism
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; D050600:SNARE Proteins; C493415:Slc6a1 protein, rat; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins; C096324:botulinum toxin type C