Glycine Transporters: Essential Regulators of Neurotransmission

Glycine has important neurotransmitter functions at inhibitory and excitatory synapses in the vertebrate central nervous system. The effective synaptic concentrations of glycine are regulated by glycine transporters (GlyTs), which mediate its reuptake into nerve terminals and adjacent glial cells. GlyTs are members of the Na(+)/Cl(-)-dependent transporter family, whose activities and subcellular distributions are regulated by phosphorylation and interactions with other proteins. The analysis of GlyT knockout mice has revealed distinct functions of individual GlyT subtypes in synaptic transmission and provided animal models for two hereditary human diseases, glycine encephalopathy and hyperekplexia. Selective GlyT inhibitors could be of therapeutic value in cognitive disorders, schizophrenia and pain.