Pathways & interactions
Sodium:neurotransmitter symporter, inebriated (IPR002944)
Short name: Na/ntran_symport_inebriated
Overlapping homologous superfamilies
- Sodium:neurotransmitter symporter superfamily (IPR037272)
- Sodium:neurotransmitter symporter (IPR000175)
- Sodium:neurotransmitter symporter, inebriated (IPR002944)
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].
On the basis of behavioural interactions with mutations in the Shaker K+ channel gene of Drosophila, mutations in a new gene, called inebriated (ine), were isolated. Considering the distinctive phenotype displayed by these flies, it was postulated that the ine mutation might increase neuronal excitability [PMID: 1334137]. Subsequently the ine mutation was mapped, and the gene was cloned. The ine gene encodes a protein of 658 amino acids with a high degree of sequence similarity to members of the Na+/Cl- -dependent neurotransmitter transporter superfamily. Therefore ine mutations may cause increased excitability of the drosophila motor neuron, as a result of defective re-uptake of its substrate neurotransmitter, the identity of which remains to be determined [PMID: 8917579]. This neurotransmitter is also important for perinerual gilial growth [PMID: 1151733] and has also been shown to act as an osmolyte transporter [PMID: 11880499].
GO:0016021 integral component of membrane
- PR01205 (INEBRIATED)