Family

Sodium:neurotransmitter symporter, creatine (IPR002984)

Short name: Na/ntran_symport_creatine

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].

A Na+ and Cl- -coupled creatine transporter has been cloned from human and rodent tissues. Initially it was mistaken for a choline transporter [PMID: 7896942, PMID: 8297374]. The creatine transporter species homologues are near identical (98% identity human vs. rat and rabbit) and they are most closely related to the transporters reported for taurine, GABA and betaine. Northern blot analysis of creatine transporter distribution reveals that the highest levels of mRNA expression are in: skeletal muscle, kidney and heart, with lower levels in brain and other tissues. Within the brain, the highest levels were detected in the cerebellum and hippocampus. This expression pattern correlates well with those tissues known to possess a high creatine uptake capacity [PMID: 7953292].

GO terms

Biological Process

GO:0006836 neurotransmitter transport

Molecular Function

GO:0005309 creatine:sodium 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