Sodium- and chloride-dependent glycine transporter 2 explained

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.^[1]

The glycine transporter 2 is a membrane protein which recaptures glycine, a major inhibitory transmitter in the spinal cord and brainstem. GlyT2 is a specific marker of glycinergic neurons and a member of the Na⁺ and Cl⁻-coupled transporter family SLC6. Glycine uptake mediated by GlyT2 is electrogenic, coupled to three Na⁺ and one Cl⁻ (i.e. two positive charges per glycine). In humans, GlyT2 is encoded by the SLC6A5 gene. Inactivation of GlyT2 in knockout mice is lethal during the second post-natal week as the absence of GlyT2 disrupts inhibitory transmission by reducing glycine release. Mutations in SLC6A5 gene are responsible for a presynaptic form of hyperekplexia, a genetic disease causing increased startle reflex. GlyT2 main physiological role is to recapture glycine released in the synaptic cleft and to maintain high glycine concentration in the presynaptic neuron. Therefore, chronic inhibition of GlyT2 will deplete intracellular storage of glycine and limit its accumulation in synaptic vesicles.^{[1] [2]}

Inhibitors

• Amoxapine
• Ethanol
• N-Arachidonylglycine (NAGly)
• Opiranserin (VVZ-149)
• ORG-25543
• VVZ-368

See also

• • Solute carrier family

Further reading

• López-Corcuera B, Aragón C, Geerlings A . Regulation of glycine transporters. . Biochem. Soc. Trans. . 29 . Pt 6 . 742–5 . 2002 . 11709067 . 10.1042/BST0290742 .
• Gallagher MJ, Burgess LH, Brunden KR . Characterization of multiple forms of the human glycine transporter type-2. . Brain Res. Mol. Brain Res. . 70 . 1 . 101–15 . 1999 . 10381548 . 10.1016/S0169-328X(99)00135-7 .
• Evans J, Herdon H, Cairns W, etal . Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter. . FEBS Lett. . 463 . 3 . 301–6 . 2000 . 10606742 . 10.1016/S0014-5793(99)01636-1 . 21445629 . free .
• Martínez-Maza R, Poyatos I, López-Corcuera B, etal . The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2. . J. Biol. Chem. . 276 . 3 . 2168–73 . 2001 . 11036075 . 10.1074/jbc.M006774200 . free .
• Geerlings A, Núñez E, Rodenstein L, etal . Glycine transporter isoforms show differential subcellular localization in PC12 cells. . J. Neurochem. . 82 . 1 . 58–65 . 2002 . 12091465 . 10.1046/j.1471-4159.2002.00930.x . 22855247 . free .
• Baliova M, Betz H, Jursky F . Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2. . J. Neurochem. . 88 . 1 . 227–32 . 2004 . 14675166 . 10.1046/j.1471-4159.2003.02192.x. 26788320 . free .
• Jamra RA, Villela AW, Klein K, etal . No association between genetic variants at the GLYT2 gene and bipolar affective disorder and schizophrenia. . Psychiatr. Genet. . 16 . 3 . 91 . 2006 . 16691125 . 10.1097/01.ypg.0000199450.07786.ab .
• Rees MI, Harvey K, Pearce BR, etal . Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. . Nat. Genet. . 38 . 7 . 801–6 . 2006 . 16751771 . 10.1038/ng1814 . 3204411.
• Roux M, Supplisson S . Neuronal and glial glycine transporters have different stoichiometries. . Neuron . 25 . 2 . 373–83 . 2000 . 10719892 . 10.1016/s0896-6273(00)80901-0. free .
• Aubrey K, Rossi FM. The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype. . J. Neurosci. . 27 . 23 . 6273–81 . 2007 . 17554001 . 10.1523/JNEUROSCI.1024-07.2007. 6672136 . etal.
• Rousseau F, Aubrey KR, Supplisson S . The glycine transporter GlyT2 controls the dynamics of synaptic vesicle refilling in inhibitory spinal cord neurons.. . J. Neurosci. . 28 . 39 . 9755–68 . 2008 . 18815261 . 10.1523/JNEUROSCI.0509-08.2008. 6671229 . free .
• Eulenburg V, Becker K, Gomeza J, etal . Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. . Biochem. Biophys. Res. Commun. . 348 . 2 . 400–5 . 2006 . 16884688 . 10.1016/j.bbrc.2006.07.080 . 27350533 .

Notes and References

1. Morrow JA, Collie IT, Dunbar DR, Walker GB, Shahid M, Hill DR . Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome . FEBS Lett. . 439 . 3 . 334–40 . November 1998 . 9845349 . 10.1016/S0014-5793(98)01390-8. 82276379 . free .
2. Web site: Entrez Gene: SLC6A5 solute carrier family 6 (neurotransmitter transporter, glycine), member 5.