Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and is responsible for most of the fast synaptic neurotransmission. Glutamate has great contribution for learning, memory, and neuronal plasticity. Dysregulation of glutamate transmission plays a role in the pathophysiology of several psychiatric and neurological diseases¹. 

Three vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3) have been identified. They are responsible for packaging and transporting glutamate into synaptic vesicles. VGLUTs in part regulate the storage and release of glutamate in excitatory circuits in the brain.

All three VGLUT isoforms are highly conserved and have the same predicted topology including 12 putative transmembrane domains. They all share a conserved dileucine-like motif in the C terminus. This motif was found to be important for VGLUT1 endocytosis. In addition, VGLUT1 contains two polyproline domains distal to the C-terminal dileucine-like motif, including one that interacts with the endocytic BAR (Bin/Amphiphysin/Rvs) domain protein endophilin. Two additional dileucine-like motifs are present in the N terminus of VGLUT1 that are not well conserved in the other isoforms^1-3. 

VGLUT1 is expressed in the hippocampus, cerebral cortex, and cerebellar cortex and appears to be the main isoform expressed in the cortex. The transporter is also detected in the enteric nervous system and pancreatic tissue. VGLUT1 has been suggested to influence the properties of the release of glutamate^1,2.