SLC18A1
Description
The SLC18A1 (solute carrier family 18 member A1) is a protein-coding gene located on chromosome 8.
Vesicular monoamine transporter 1 (VMAT1), also known as chromaffin granule amine transporter (CGAT) or solute carrier family 18 member 1 (SLC18A1), is a protein that in humans is encoded by the SLC18A1 gene. VMAT1 is an integral membrane protein, which is embedded in synaptic vesicles and serves to transfer monoamines, such as norepinephrine, epinephrine, dopamine, and serotonin, between the cytosol and synaptic vesicles. SLC18A1 is an isoform of the vesicular monoamine transporter. The idea that there must be specific transport proteins associated with the uptake of monoamines and acetylcholine into vesicles developed due to the discovery of specific inhibitors which interfered with monoamine neurotransmission and also depleted monoamines in neuroendocrine tissues. VMAT1 and VMAT2 were first identified in rats upon cloning cDNAs for proteins which gave non-amine accumulating recipient cells the ability to sequester monoamines. Subsequently, human VMATs were cloned using human cDNA libraries with the rat homologs as probes, and heterologous-cell amine uptake assays were performed to verify transport properties. Across mammalian species, VMATs have been found to be structurally well conserved; VMAT1s have an overall sequence identity exceeding 80%. However, there exists only a 60% sequence identity between the human VMAT1 and VMAT2. VMAT1 is an acidic glycoprotein with an apparent weight of 40 kDa. Although the crystallographic structure has not yet been fully resolved, VMAT1 is known to have either twelve transmembrane domains (TMDs), based on Kyte-Doolittle hydrophobicity scale analysis or ten TMDs, based on MAXHOM alignment.
[Isoform 1]: An electrogenic antiporter that exchanges one cationic monoamine for two intravesicular protons across the membrane of secretory and synaptic vesicles. This protein utilizes the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. It transports catecholamines and indolamines, with a higher affinity for serotonin (PubMed:23337945, PubMed:8643547, PubMed:16326835). This transporter regulates the transvesicular monoaminergic gradient that determines the quantal size. It mediates presynaptic monoaminergic vesicle transport in the amygdala and prefrontal brain regions, which are involved in emotion processing in response to environmental stimuli (PubMed:23337945). {ECO:0000269|PubMed:16326835, ECO:0000269|PubMed:23337945, ECO:0000269|PubMed:8643547}.
SLC18A1 is also known as CGAT, VAT1, VMAT1.
