“Neurotransmitter sodium symporter”的意思、由来-开放百科全书

A neurotransmitter sodium symporter (NSS) (TC# 2.A.22) is type of neurotransmitter transporter that catalyzes the uptake of a variety of neurotransmitters, amino acids, osmolytes and related nitrogenous substances by a solute:Na⁺ symport mechanism.^[1]^[2] 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 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.^[3]

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.

Neurotransmitter sodium symporters (NSS) are targets for anti-depressants, psychostimulants and other drugs.^[4]

Transport reaction

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.^[2]

NSS carriers are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport (see 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⁻.^[5] In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters.^[6]^[7] 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.^[8]

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.^[9]

Crystal structures

There are several crystal structures available for a couple members of the NSS family:

Subfamilies

Several characterized proteins are classified within the NSS family and can be found in the Transporter Classification Database.

Human proteins containing this domain

See also

References

1. ^{{cite journal|last1=Rudnick|first1=G|last2=Krämer|first2=R|last3=Blakely|first3=RD|last4=Murphy|first4=DL|last5=Verrey|first5=F|title=The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction.|journal=Pflügers Archiv|date=January 2014|volume=466|issue=1|pages=25–42|doi=10.1007/s00424-013-1410-1|pmid=24337881|pmc=3930102|url=http://www.zora.uzh.ch/94232/1/Rudnick_et_al-SLC6_transporters.pdf}}
2. ^¹²{{cite web|last1=Saier|first1=MH Jr|title=2.A.22 The Neurotransmitter:Sodium Symporter (NSS) Family|url=http://www.tcdb.org/search/result.php?tc=2.A.22#ref10492|website=Transporter Classification Database}}
3. ^{{cite journal |vauthors=Attwell D, Bouvier M |title=Cloners quick on the uptake |journal=Curr. Biol. |volume=2 |issue=10 |pages=541–543 |year=1992 |pmid=15336049 |doi=10.1016/0960-9822(92)90024-5}}
4. ^{{cite journal|last1=Zomot|first1=E|last2=Bendahan|first2=A|last3=Quick|first3=M|last4=Zhao|first4=Y|last5=Javitch|first5=JA|last6=Kanner|first6=BI|title=Mechanism of chloride interaction with neurotransmitter:sodium symporters.|journal=Nature|date=October 11, 2007|volume=449|issue=7163|pages=726–30|pmid=17704762|doi=10.1038/nature06133}}
5. ^{{cite journal |vauthors=Malandro MS, Kilberg MS |title=Molecular biology of mammalian amino acid transporters |journal=Annu. Rev. Biochem. |volume=65 |issue= |pages=305–336 |year=1996 |pmid=8811182 |doi=10.1146/annurev.bi.65.070196.001513}}
6. ^{{cite journal |vauthors=Arriza JL, Amara SG |title=Neurotransmitter transporters: three distinct gene families |journal=Curr. Opin. Neurobiol. |volume=3 |issue=3 |pages=337–344 |year=1993 |pmid=8103691 |doi=10.1016/0959-4388(93)90126-J}}
7. ^{{cite journal |vauthors=Uhl GR, Johnson PS |title=Neurotransmitter transporters: three important gene families for neuronal function |journal=J. Exp. Biol. |volume=196 |issue= |pages=229–236 |year=1994 |pmid=7823024}}
8. ^{{cite journal |vauthors=Nelson N, Lill H |title=Homologies and family relationships among Na⁺/Cl⁻ neurotransmitter transporters |journal=Meth. Enzymol. |volume=296 |issue= |pages=425–436 |year=1998 |pmid=9779464 |doi=10.1016/S0076-6879(98)96030-X |series=Methods in Enzymology |isbn=978-0-12-182197-5}}
9. ^{{cite journal|last1=Tavoulari|first1=S|last2=Rizwan|first2=AN|last3=Forrest|first3=LR|last4=Rudnick|first4=G|title=Reconstructing a chloride-binding site in a bacterial neurotransmitter transporter homologue.|journal=Journal of Biological Chemistry|date=January 28, 2011|volume=286|issue=4|pages=2834–42|doi=10.1074/jbc.M110.186064|pmid=21115480|pmc=3024779}}