VGLUT3 (Vesicular Glutamate Transporter 3), encoded by the SLC17A8 gene, is a unique vesicular glutamate transporter expressed primarily in cholinergic and serotonergic neurons, as well as some GABAergic neurons. [1] Unlike VGLUT1 and VGLUT2, which are restricted to classical glutamatergic neurons, VGLUT3 is expressed in neurons that use other classical neurotransmitters. This "cotransmission" role means VGLUT3 packages glutamate alongside acetylcholine, serotonin, or GABA, enabling these neurons to also release glutamate as a cotransmitter. [2] VGLUT3 is essential for hearing and has critical neuromodulatory functions in basal ganglia and mood-related circuits.
| Property | Value |
|---|---|
| Symbol | VGLUT3 (SLC17A8) |
| Full Name | Vesicular Glutamate Transporter 3 |
| Chromosomal Location | 12q23.1 |
| NCBI Gene ID | 51287 |
| Ensembl ID | ENSG00000101190 |
| UniProt ID | Q9P0U8 |
| Aliases | VGLUT3, SLC17A8, BNPI |
VGLUT3 is a member of the solute carrier family 17 (SLC17), which includes vesicular glutamate transporters and phosphate transporters:
VGLUT3 transports glutamate into synaptic vesicles: [3]
Unlike VGLUT1 and VGLUT2:
VGLUT3 enables neurotransmitter cotransmission: [2:1]
VGLUT3 is essential for auditory neurotransmission: [4]
VGLUT3 in cholinergic neurons regulates basal ganglia: [5]
VGLUT3 is implicated in PD pathophysiology: [6][7]
VGLUT3 mutations cause progressive hearing loss: [8][4:1]
VGLUT3 in serotonergic neurons modulates mood: [10]
VGLUT3 in basal forebrain cholinergic system: [11]
VGLUT3 linked to various conditions: [12]
VGLUT3 is expressed in specific neuronal populations:
| Brain Region | Neuron Type |
|---|---|
| Striatum | Cholinergic interneurons |
| Pedunculopontine nucleus | Cholinergic neurons |
| Laterodorsal tegmental nucleus | Cholinergic neurons |
| Dorsal raphe | Serotonergic neurons |
| Inner ear | Hair cells |
| Brain Region | Neuron Type |
|---|---|
| Basal forebrain | Cholinergic projection neurons |
| Cortex | Some GABAergic interneurons |
| Hippocampus | Specific interneuron populations [14] |
Gene therapy approaches show promise: [9:1]
Fremeau RT Jr, et al. The identification of VGLUT3 defines a novel population of glutamatergic neurons. Proceedings of the National Academy of Sciences. 2004. ↩︎
Zhang S, et al. VGLUT3 and neurotransmitter co-release. Neuron. 2015. ↩︎ ↩︎
Gras C, et al. VGLUT3 is a vesicular glutamate transporter with unique properties. Journal of Neuroscience. 2008. ↩︎
Seal RP, et al. VGLUT3 is essential for hearing and auditory processing. Nature. 2007. ↩︎ ↩︎
Gilleron J, et al. VGLUT3 in cholinergic neurons regulates basal ganglia function. Journal of Neurochemistry. 2011. ↩︎
Shao Y, et al. VGLUT3 in Parkinson's disease and movement disorders. Movement Disorders. 2014. ↩︎
Liu Y, et al. VGLUT3 and alpha-synuclein in PD models. Acta Neuropathologica. 2021. ↩︎ ↩︎
Nagy K, et al. VGLUT3 mutations cause hearing loss and auditory neuropathy. Molecular Genetics and Genomics. 2016. ↩︎
Akil O, et al. VGLUT3 gene therapy for hearing loss. Molecular Therapy. 2019. ↩︎ ↩︎
Amilhon B, et al. VGLUT3 in serotonergic neurons modulates mood and behavior. Journal of Neuroscience. 2010. ↩︎
Mendes MS, et al. VGLUT3 in cholinergic basal forebrain and Alzheimer's disease. Journal of Alzheimer's Disease. 2019. ↩︎
Blakely RD, et al. VGLUT3 and neuropsychiatric disorders. Nature Reviews Neuroscience. 2012. ↩︎
Shen HW, et al. VGLUT3 and cocaine reward. Neuropsychopharmacology. 2018. ↩︎
Toth K, et al. VGLUT3 in the hippocampus. Hippocampus. 2019. ↩︎