Pathways & interactions
Sodium:neurotransmitter symporter, GABA, GAT-3 (IPR002982)
Short name: Na/ntran_symport_GABA_GAT3
- Sodium:neurotransmitter symporter (IPR000175)
- Sodium:neurotransmitter symporter, GABA, GAT-3 (IPR002982)
Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity transport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions [PMID: 15336049]. Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na+ and Cl-, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport. The latter couple glutamate and aspartate uptake to the cotransport of Na+ and the counter-transport of K+, with no apparent dependence on Cl- [PMID: 8811182]. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters [PMID: 8103691, PMID: 7823024].
Sequence analysis of the Na+/Cl- neurotransmitter superfamily reveals that it can be divided into four subfamilies, these being transporters for monoamines, the amino acids proline and glycine, GABA, and a group of orphan transporters [PMID: 9779464].
GABA is the major inhibitory transmitter in the mammalian brain, and is widely distributed throughout the nervous system. Molecular cloning studies have resulted in the cloning of three Na+ and Cl- -coupled GABA transporters (known as GAT-1, GAT-2, GAT-3) and a betaine/GABA transporter (BGT-1). Each transporter shows varying affinities for GABA, different substrate and blocker pharmacologies, and different tissue localisation [PMID: 8774941]. Brain regions containing GAT-3 mRNA transcripts include the retina, olfactory bulb, subfornical organ, hypothalamus, midline thalamus and brainstem. GAT-3 mRNA was found to be absent from the neocortex and cerebellar cortex, and very weak in the hippocampus [PMID: 8774941]. Furthermore, immunocytological studies have demonstrated that this transporter may be localised solely to glial (non-neuronal) cells, suggesting that glial GABA uptake may function to limit the spread of GABA from the synapse, as well as to regulate overall GABA levels.
- PR01197 (GAT3TRNSPORT)