Glycine Transporters

Glycine transporters (GlyTs) belong to a family of high affinity Na⁺- and Cl^--dependent neurotransmitter transporters proteins. There are two subtypes of glycine transporters; GlyT1 and GlyT2.

GlyT1s are predominantly located on glia within caudal brain areas, the diencephalon and olfactory bulb. They regulate synaptic glycine concentration, influencing NMDA receptor-mediated neurotransmission and are important in neonatal life for regulating glycine concentrations at inhibitory glycinergic synapses. GlyT2s are predominantly located on neurons within caudal brain areas, the spinal cord, brainstem and cerebellum. They are crucial for efficient transmitter loading of synaptic vesicles and lack-of-function mutations are fatal in the early neonatal period. Both GlyT1 and GlyT2 are unevenly distributed across the cell surface, which is thought to optimize the removal of glycine from the extracellular compartment.

Transport of glycine involves co-transport of Na⁺ and Cl^- ions. The Na⁺ concentration gradient is maintained by the plasma membrane Na⁺,K⁺-ATPase and allows the accumulation of glycine against its concentration gradient. GlyTs are glycosylated and this is necessary for the protein trafficking to the plasma membrane. Further regulatory mechanisms of GlyTs include the presence of PKC, PKA and CaMK consensus sites, pH and syntaxin1 levels.

Pharmacologically, glycine transporter inhibitors may have applications in the treatment of muscle tone defects, epilepsy, schizophrenia, pain and neurodegenerative disorders.

External sources of pharmacological information for Glycine Transporters :

• IUPHAR Receptor Code

• BJP Guide

Glycine Transporter Gene Data