Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A.
Syntaxin 1A inhibits GABA uptake of an endogenous GABA transporter in neuronal cultures from rat hippocampus and in reconstitution systems expressing the cloned rat brain GABA transporter GAT1. Evidence of interactions between syntaxin 1A and GAT1 comes from three experimental approaches: botulinum toxin cleavage of syntaxin 1A, syntaxin 1A antisense treatments, and coimmunoprecipitation of a complex containing GAT1 and syntaxin 1A. Protein kinase C (PKC), shown previously to modulate GABA transporter function, exerts its modulatory effects by regulating the availability of syntaxin 1A to interact with the transporter, and a transporter mutant that fails to interact with syntaxin 1A is not regulated by PKC. These results suggest a new target for regulation by syntaxin 1A and a novel mechanism for controlling the machinery involved in both neurotransmitter release and reuptake.
Beckman
M L
ML
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA.
Bernstein
E M
EM
Quick
M W
MW
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D001905:Botulinum Toxins / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D027361:Organic Anion Transporters; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000502:physiology; D050827:Syntaxin 1
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; C493415:Slc6a1 protein, rat; D015222:Sodium Channels; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D011493:Protein Kinase C; D001905:Botulinum Toxins