A neurotransmitter sodium symporter (NSS)
TC# 2.A.22
is type of

neurotransmitter transporter Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intr ...

that catalyzes the uptake of a variety of neurotransmitters, amino acids, osmolytes and related nitrogenous substances by a solute:Na⁺ symport mechanism. The NSS family is a member of the APC superfamily. Its constituents have been found in bacteria, archaea and eukaryotes.

Function

Neurotransmitter transport systems are responsible for the release, re-uptake and recycling of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

s at

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

s. High affinity transport proteins found in the plasma membrane of

presynaptic In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

nerve terminals and

glial cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...

s are responsible for the removal, from the extracellular space, of released-transmitters, thereby terminating their actions. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the

co-transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

of Na⁺ and Cl⁻, in order to transport neurotransmitter molecules into the cell against their concentration gradient. Neurotransmitter sodium symporters (NSS) are targets for anti-depressants, psychostimulants and other drugs.

Transport reaction

The generalized transport reaction for the members of this family is: ::solute (out) + Na⁺ (out) → solute (in) + Na⁺ (in).

Structure

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, taurine and other small molecules. NSS carriers are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport (se
TC# 2.A.23
. The latter couple glutamate and aspartate uptake to the cotransport of Na⁺ and the counter-transport of K⁺, with no apparent dependence on Cl⁻. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters. 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. Tavoulari et al. (2011) described conversion of the Cl⁻ -independent prokaryotic tryptophan transporter TnaT
2.A.22.4.1
to a fully functional Cl⁻ -dependent form by a single point mutation, D268S. Mutations in TnaT-D268S, in wild type TnaT and in a serotonin transporter
SERT; 2.A.22.1.1
provided direct evidence for the involvement of each of the proposed residues in Cl⁻ coordination. In both SERT and TnaT-D268S, Cl⁻ and Na⁺ mutually increase each other's potency, consistent with am electrostatic interaction through adjacent binding sites.

Crystal structures

There are several crystal structures available for a couple members of the NSS family: * 2.A.22.1.7 - Dopamine transporter: , , , , * 2.A.22.4.2 - The amino acid (leucine):2 Na+ symporter, LeuTAa: , , , , , , ,
more

Subfamilies

Taurine transporter Taurine (), or 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. It ...

()

Human proteins containing this domain

SLC6A1 GABA transporter 1 (GAT1) also known as sodium- and chloride-dependent GABA transporter 1 is a protein that in humans is encoded by the ''SLC6A1'' gene and belongs to the solute carrier 6 (SLC6) family of transporters. It mediates gamma-aminobutyr ...

, SLC6A2, SLC6A3,

SLC6A4 The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

SLC6A5 Sodium- and chloride-dependent glycine transporter 2, also known as glycine transporter 2 (GlyT2), is a protein that in humans is encoded by the ''SLC6A5'' gene. The glycine transporter 2 is a membrane protein which recaptures glycine, a major in ...

SLC6A6 Sodium- and chloride-dependent taurine transporter is a protein that in humans is encoded by the ''SLC6A6'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity... ...

, SLC6A7,

SLC6A8 Sodium- and chloride-dependent creatine transporter 1 is a protein that in humans is encoded by the ''SLC6A8'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity ...

, SLC6A9, SLC6A11,

SLC6A12 Sodium- and chloride-dependent betaine transporter, also known as Na(+)/Cl(-) betaine/GABA transporter (BGT-1), is a protein that in humans is encoded by the ''SLC6A12'' gene. BGT-1 is predominantly expressed in the liver (hepatocytes). It is also ...

, SLC6A13,

SLC6A14 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) (SLC6A14) is a protein that in humans is encoded by the ''SLC6A14'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describ ...

, SLC6A15, SLC6A16, SLC6A17,

SLC6A18 Solute carrier family 6, member 18 also known as SLC6A18 is a protein which in humans is encoded by the ''SLC6A18'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of her ...

SLC6A19 Sodium-dependent neutral amino acid transporter B(0)AT1 is a protein that in humans is encoded by the ''SLC6A19'' gene. Function SLC6A19 is a system B(0) transporter that mediates epithelial resorption of neutral amino acids across the apica ...

SLC6A20 Solute carrier family 6, member 20 also known as SLC6A20 is a protein which in humans is encoded by the ''SLC6A20'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of her ...

References

External links

Transporter Classification Database
(tcdb.org) for more detailed description of this family {{Portal bar, Biology, border=no Protein domains Protein families Membrane proteins Transport proteins Integral membrane proteins Transmembrane proteins Transmembrane transporters Protein pages needing a picture