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. Discovery 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. Structure 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. MAXHOM alignment was determined using the "profile-fed neural network systems from Heidelberg" (PHD) program. The main difference between these two models arises from the placement of TMDs II and IV in the vesicle lumen or the cytoplasm. Localization Cell types VMATs are found in a variety of cell types throughout the body, however, VMAT1 is found exclusively in neuroendocrine cells, in contrast to VMAT2, which is also found in the PNS and CNS. Specifically, VMAT1 is found in chromaffin cells, enterochromaffin cells, and small intensely fluorescent cells (SIFs). Chromaffin cells are responsible for releasing the catecholamines (norepinephrine and epinephrine) into systemic circulation. Enterochromaffin cells are responsible for storing serotonin in the gastrointestinal tract. SIFs are interneurons associated with the sympathetic nervous system which are managed by dopamine. Vesicles VMAT1 is found in both large dense-core vesicles (LDCVs) as well as in small synaptic vesicles (SSVs). This was discovered via studying rat adrenal medulla cells (PC12 cells). LDCVs are