Neurotransmitter sodium symporter (NSS)

A neurotransmitter sodium symporter (NSS) is a type of membrane transporter that mediates the sodium- and chloride-dependent reuptake of small-molecule neurotransmitters from the synaptic cleft into presynaptic neurons or surrounding glia[1][3][5][7][9]. Members of the NSS family, also referred to as solute carrier family 6 (SLC6), include transporters for serotonin (SERT), dopamine (DAT), norepinephrine (NET), glycine (GlyT), and GABA (GAT)[3][7][9]. These transporters terminate neurotransmission and recycle neurotransmitters for reuse, playing a pivotal role in CNS function and homeostasis[1][5][9]. Alterations in NSS activity have been implicated in multiple psychiatric and neurological disorders, making them key therapeutic targets for antidepressants, psychostimulants, and drugs of abuse[3][4][9]. They share a structural fold composed of 12 transmembrane helices and operate via a sodium/chloride-dependent symport mechanism, utilizing ionic gradients to drive active neurotransmitter uptake against concentration gradients[2][4][6].

Other names

Solute carrier family 6 transporter (SLC6 transporter)Neurotransmitter:sodium symporterSodium-dependent neurotransmitter transporterMonoamine transporter (monoamine-specific members, e.g. DAT, SERT, NET)SLC6 family transporter

Inhibition of neurotransmitter reuptake (competitive/noncompetitive), Blockade of transporter binding sites, Substrate reversal or efflux (e.g., amphetamines), Allosteric modulation of transporter conformation