Sodium- and chloride-dependent glycine transporter 2, also known as glycine transporter 2 (GlyT2), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''SLC6A5''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The glycine transporter 2 is a membrane protein which recaptures

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

, a major inhibitory transmitter in the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

and

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

. 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''

. Inactivation of GlyT2 in

knockout A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...

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 Hyperekplexia (; "exaggerated surprise") is a very rare neurologic disorder classically characterised by pronounced startle responses to tactile or acoustic stimuli and hypertonia. The hypertonia may be predominantly truncal, attenuated during ...

, a genetic disease causing increased

startle In animals, including humans, the startle response is a largely unconscious defensive response to sudden or threatening stimuli, such as sudden noise or sharp movement, and is associated with negative affect.Rammirez-Moreno, David. "A computation ...

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.

Inhibitors

Amoxapine Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 ...

Ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

* N-Arachidonylglycine (NAGly) * Opiranserin (VVZ-149) * ORG-25543 * VVZ-368

Inhibitors

See also

References

Further reading