Family

Sodium:neurotransmitter symporter, glycine, type 1 (IPR003028)

Short name: Na/ntran_symport_glycine_GLY1

Family relationships

Description

Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity transport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions [PMID: 15336049]. Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na+ and Cl-, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport. The latter couple glutamate and aspartate uptake to the cotransport of Na+ and the counter-transport of K+, with no apparent dependence on Cl- [PMID: 8811182]. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters [PMID: 8103691, PMID: 7823024].

Sequence analysis of the Na+/Cl- neurotransmitter superfamily reveals that it can be divided into four subfamilies, these being transporters for monoamines, the amino acids proline and glycine, GABA, and a group of orphan transporters [PMID: 9779464].

Glycine is known to serve two contrasting roles as a neurotransmitter in the central nervous system. Firstly, it serves as an inhibitory neurotransmitter in the spinal cord, brainstem and retina, where it activates a ligand-gated Cl- channel. Secondly, it is an obligatory co-agonist for activation of the N-methyl-D-aspartate (NMDA) receptor - unless glycine is also bound to the NMDA receptor, glutamate cannot activate this ion channel. Not surprisingly, then, plasma membranes possess glycine transporters in order to regulate its concentration. Two independent genes have been identified that encode Na+ and Cl- -coupled glycine transporters. Their products, referred to as GLYT-1 and GLYT-2, have differing distribution patterns within the central nervous system, suggesting they may subserve unique functions [PMID: 8811182]. Indeed the distribution of the GLYT-1 transporter suggests it may play a role in regulating glycine concentrations in brain regions containing glycine-dependent NMDA receptors [PMID: 8226790]. Three different mRNA isoforms for GLYT-1 have been detected. These arise as a result of differential splicing, or the usage of multiple promoter sites. They encode transporters of 633, 638 and 692 amino acid residues, all three having 50-60% similarity to other transporters in the Na+ and Cl- -coupled neurotransmitter transporter superfamily.

GO terms

Biological Process

GO:0006836 neurotransmitter transport

Molecular Function

GO:0005283 sodium:amino acid symporter activity

Cellular Component

GO:0005887 integral component of plasma membrane
GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS