SLC6 neurotransmitter transporter family

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Members of the solute carrier family 6 (SLC6) of sodium- and (sometimes chloride-) dependent neurotransmitter transporters [13,20,51] are primarily plasma membrane located and may be divided into four subfamilies that transport monoamines, GABA, glycine and neutral amino acids, plus the related bacterial NSS transporters [69]. The members of this superfamily share a structural motif of 10 TM segments that has been observed in crystal structures of the NSS bacterial homolog LeuTAa, a Na+-dependent amino acid transporter from Aquiflex aeolicus [90] and in several other transporter families structurally related to LeuT [31].

Monoamine transporter subfamily

Overview

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Monoamine neurotransmission is limited by perisynaptic transporters. Presynaptic monoamine transporters allow recycling of synaptically released noradrenaline, dopamine and 5-hydroxytryptamine (5-HT).

Transporters

NET (NET / SLC6A2) Show summary » More detailed page

DAT (DAT / SLC6A3) Show summary » More detailed page

SERT (SERT / SLC6A4) Show summary » More detailed page

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GABA transporter subfamily

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The activity of GABA-transporters located predominantly upon neurones (GAT-1), glia (GAT-3) or both (GAT-2, BGT-1) serves to terminate phasic GABA-ergic transmission, maintain low ambient extracellular concentrations of GABA, and recycle GABA for reuse by neurones. Nonetheless, ambient concentrations of GABA are sufficient to sustain tonic inhibition mediated by high affinity GABAA receptors in certain neuronal populations [72]. GAT1 is the predominant GABA transporter in the brain and occurs primarily upon the terminals of presynaptic neurones and to a much lesser extent upon distal astocytic processes that are in proximity to axons terminals. GAT3 resides predominantly on distal astrocytic terminals that are close to the GABAergic synapse. By contrast, BGT1 occupies an extrasynaptic location possibly along with GAT2 which has limited expression in the brain [56]. TauT is a high affinity taurine transporter involved in osmotic balance that occurs in the brain and non-neuronal tissues, such as the kidney, brush border membrane of the intestine and blood brain barrier [20,41]. CT1, which transports creatine, has a ubiquitous expression pattern, often co-localizing with creatine kinase [20].

Transporters

GAT1 (GAT1 / SLC6A1) Show summary » More detailed page

GAT2 (GAT2 / SLC6A13) Show summary »

GAT3 (GAT3 / SLC6A11) Show summary »

BGT1 (BGT1 / SLC6A12) Show summary »

TauT (TauT / SLC6A6) Show summary »

CT1 (CT1 / SLC6A8) Show summary »

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Glycine transporter subfamily

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Two gene products, GlyT1 and GlyT2, are known that give rise to transporters that are predominantly located on glia and neurones, respectively. Five variants of GlyT1 (a,b,c,d & e) differing in their N- and C-termini are generated by alternative promoter usage and splicing, and three splice variants of GlyT2 (a,b & c) have also been identified (see [8,29,36,76] for reviews). GlyT1 transporter isoforms expressed in glia surrounding glutamatergic synapses regulate synaptic glycine concentrations influencing NMDA receptor-mediated neurotransmission [7,34], but also are important, in early neonatal life, for regulating glycine concentrations at inhibitory glycinergic synapses [37]. Homozygous mice engineered to totally lack GlyT1 exhibit severe respiratory and motor deficiencies due to hyperactive glycinergic signalling and die within the first postnatal day [37,80]. Disruption of GlyT1 restricted to forebrain neurones is associated with enhancement of EPSCs mediated by NMDA receptors and behaviours that are suggestive of a promnesic action [91]. GlyT2 transporters localised on the axons and boutons of glycinergic neurones appear crucial for efficient transmitter loading of synaptic vesicles but may not be essential for the termination of inhibitory neurotransmission [38,67]. Mice in which GlyT2 has been deleted develop a fatal hyperekplexia phenotype during the second postnatal week [38] and mutations in the human gene encoding GlyT2 (SLC6A5) have been identified in patients with hyperekplexia (reviewed by [42]). ATB0+ (SLCA14) is a transporter for numerous dipolar and cationic amino acids and thus has a much broader substrate specificity than the glycine transporters alongside which it is grouped on the basis of structural similarity [20]. ATB0+ is expressed in various peripheral tissues [20]. By contrast PROT (SLC6A7), which is expressed only in brain in association with a subset of excitatory nerve terminals, shows specificity for the transport of L-proline.

Transporters

GlyT1 (GlyT1 / SLC6A9) Show summary »

GlyT2 (GlyT2 / SLC6A5) Show summary »

ATB0,+ (ATB0,+ / SLC6A14) Show summary »

PROT (PROT / SLC6A7) Show summary »

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Neutral amino acid transporter subfamily

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Certain members of neutral amino acid transport family are expressed upon the apical surface of epithelial cells and are important for the absorption of amino acids from the duodenum, jejunum and ileum and their reabsorption within the proximal tubule of the nephron (i.e. B0AT1 (SLC6A19), SLC6A17, SLC6A18, SLC6A20). Others may function as transporters for neurotransmitters or their precursors (i.e. B0AT2, SLC6A17) [14].

Transporters

B0AT1 (B0AT1 / SLC6A19) Show summary »

B0AT2 (B0AT2 / SLC6A15) Show summary »

B0AT3 (B0AT3 / SLC6A18) Show summary »

NTT5 / SLC6A16 Show summary »

NTT4 / SLC6A17 Show summary »

SIT1 (SIT1 / SLC6A20) Show summary »

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Further reading

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References

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