GABA transporter 2 (GAT2; SLC6A13) also known as sodium- and chloride-dependent GABA transporter 2 is one of four GABA transporters, GAT1 ( SLC6A1), GAT2 (SLC6A13), GAT3 ( SLC6A11) and BGT1 ( SLC6A12). Note that GAT2 is different from BGT1 despite the fact that the latter transporter is sometimes referred at as (mouse) GAT-2. All these transporters are highly hydrophobic proteins with 12 transmembrane segments, extracellular glycosylation sites, and intracellular consensus sites for phosphorylation, and there is over 50% amino acid homology between each of them. Each binds GABA with varying affinities with BGT1 having the lowest affinity and GAT3 the highest. GAT2 (SLC6A13) is predominantly expressed in hepatocytes in the liver, but is also found in proximal tubules in the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

as well as in the

leptomeninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...

and in some blood vessels in the brain.

Biological function

Brain

Deletion of the GAT2 gene in mice does not appear to have any dramatic effects on brain function in a normal situation. The only difference noted so far is a slight elevation of brain

Taurine 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. I ...

levels. This was an unexpected finding, but is in agreement with the notion that GAT2 permits efflux of GABA and taurine from the brain to circulating blood through the blood brain barrier. GAT1 and GAT3 have higher concentrations in the brain and have higher affinity to GABA. This makes them more likely than GAT2 to influence the activity of neurotransmitter GABA in the brain.

Liver

GAT2 is expressed in hepatocytes and is well positioned to take up GABA entering the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

from the intestine (via the portal vein), but it is not known if this is an important function. On the other hand, GAT2 is also able to transport taurine and it appears to be the major taurine transporter in the liver.

Kidneys

GAT2 is also present in

proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal strai ...

s in the kidney cortex, but only in the basolateral membranes. The physiological function is unknown.

Clinical significance

The clinical significance of GAT2 is at present undetermined. Some anticonvulsants have been reported to act upon the GABA transporters. There is evidence to suggest that GABA transporters are linked to

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

, affective disorders, and

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

. But considering that GAT1 and GAT3 are expressed at far higher levels in brain tissue, it is likely that inhibition of these transporters will have a far greater anticonvulsant effect than inhibition of GAT2 and BGT1.

References

* * {{GABA metabolism and transport modulators Human proteins Neurotransmitter transporters Solute carrier family GABA