VGLUT3 Protein is a protein encoded by the SLC17A7 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
:: infobox .infobox-protein
VGLUT3 (Vesicular Glutamate Transporter 3)
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; Gene
: SLC17A7
; UniProt ID
: Q9P2F6
; PDB Structures
: Not available
; Molecular Weight
: ~62 kDa (human)
; Subcellular Localization
: Synaptic vesicles of glutamatergic and modulatory neurons
; Protein Family
: Vesicular glutamate transporter (VGLUT) family
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VGLUT3 (SLC17A7) is a 545-amino acid transmembrane protein that functions as a vesicular glutamate transporter. Unlike VGLUT1 and VGLUT2, VGLUT3 is expressed in neurons that use other neurotransmitters (monoamines, acetylcholine, GABA), making it a marker of "cotransmission" [1].
- 12 transmembrane domains: Characteristic of the major facilitator superfamily
- Proton gradient coupling: Uses V-ATPase-generated H+ gradient for transport
- Alternative expression: Found in non-classical glutamatergic neurons
VGLUT3 has a unique role in neurotransmitter co-release:
- Cotransmission: Enables glutamate release from traditionally non-glutamatergic neurons [1]
- Modulatory signaling: Expressed in cholinergic, serotonergic, and GABAergic neurons [1]
- Synaptic plasticity: Influences plasticity in circuits using corelease [1]
- Brain distribution: Cortex, hippocampus, basal ganglia, raphe nuclei [1]
VGLUT3 is expressed in:
- Subset of cholinergic neurons (basal forebrain)
- Serotonergic neurons (raphe nuclei)
- GABAergic interneurons
- Some hypothalamic neurons
VGLUT3 dysfunction is implicated in AD pathogenesis [2]:
- Cholinergic vulnerability: VGLUT3 in cholinergic neurons affected in AD [2]
- Cotransmission loss: Diminished glutamate-ACh corelease [2]
- Synaptic dysfunction: Contributes to cognitive decline [2]
- Serotonergic dysfunction: VGLUT3 in raphe neurons affected in PD [3]
- Non-motor symptoms: Contributes to depression and anxiety [3]
- Dopamine interactions: Cross-talk with dopaminergic circuits [3]
- Glutamatergic theory: VGLUT3 alterations contribute to glutamate dysfunction [4]
- Cognitive deficits: Affects cortical circuits [4]
¶ Depression and Anxiety
- Serotonergic system: VGLUT3 in raphe-cortical projections [5]
- Mood regulation: Altered glutamate-serotonin cotransmission [5]
- Excitatory-inhibitory balance: VGLUT3 affects network excitability [1]
- Seizure susceptibility: Altered in epileptic tissue [1]
- VGLUT3 enhancers: Boosting glutamate-ACh corelease
- Cotransmission modulation: Combined therapeutic approaches
- Serotonergic targeting: VGLUT3 in antidepressant mechanisms
- Novel antidepressants: Targeting glutamatergic-serotonergic interactions
- VGLUT3-Cre mice: Genetic access to specific neuronal populations
- Reporter lines: Visualization of VGLUT3-expressing neurons