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Glycine transporters (GlyTs) are members of the Na+/Cl--dependent transporter family, whose activities and subcellular distributions are regulated by phosphorylation and interactions with other proteins. GlyTs comprise glycine transporter type 1 (SLC6A9; GlyT1) and glycine transporter type 2 (SLC6A5; Glyt2). Both GlyTs exist in multiple splice variants. GlyTs that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia.
GlyT1 and GlyT2 are expressed on both astrocytes and neurons, but their expression pattern in brain tissue is foremost related to neurotransmission. GlyT2 is markedly expressed in brainstem, spinal cord and cerebellum, where it is responsible for glycine uptake into glycinergic and GABAergic terminals. GlyT1 is abundant in neocortex, thalamus and hippocampus, where it is expressed in astrocytes, and involved in glutamatergic neurotransmission. GlyT1 and GlyT2, which are located in glial cells and neurons, respectively play important roles by clearing synaptically released glycine or supplying glycine to glycinergic neurons to regulate glycinergic neurotransmission. Thus, inhibition of GlyTs could be used to modify pain signal transmission in the spinal cord.
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