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

Nat Neurosci. 2000 Oct;3(10):998-1003. doi: 10.1038/79939.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / drug effects
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Botulinum Toxins / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Cricetinae
  • GABA Plasma Membrane Transport Proteins
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Oocytes
  • Organic Anion Transporters*
  • Protein Structure, Tertiary / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • RNA, Messenger / pharmacology
  • Rats
  • Synaptic Membranes / metabolism*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Syntaxin 1
  • Xenopus
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Antigens, Surface
  • Carrier Proteins
  • GABA Plasma Membrane Transport Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Organic Anion Transporters
  • RNA, Messenger
  • Slc6a1 protein, rat
  • Stx1a protein, rat
  • Syntaxin 1
  • gamma-Aminobutyric Acid
  • Botulinum Toxins