VGLUT2 Protein is a protein encoded by the SLC17A6 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
:: infobox .infobox-protein
VGLUT2 (Vesicular Glutamate Transporter 2)
: -
; Gene
: SLC17A6
; UniProt ID
: Q9P0U4
; PDB Structures
: 5W5C, 7SKQ
; Molecular Weight
: ~65 kDa (human)
; Subcellular Localization
: Synaptic vesicles of glutamatergic neurons
; Protein Family
: Vesicular glutamate transporter (VGLUT) family
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VGLUT2 (SLC17A6) is a 582-amino acid transmembrane protein that functions as a proton-coupled glutamate transporter into synaptic vesicles. The protein features:
- 12 transmembrane domains: Characteristic of the major facilitator superfamily
- Vesicular lumen orientation: Transports glutamate into the vesicle lumen
- Proton gradient coupling: Uses V-ATPase-generated H+ gradient for transport
- Oligomerization: Functions as a homodimer
The transporter couples the proton gradient (H+ influx) to glutamate uptake against its concentration gradient.
VGLUT2 is essential for glutamatergic neurotransmission and vesicle filling:
- Glutamate packaging: Packages glutamate into synaptic vesicles for release [1]
- Vesicular filling: Determines quantal size of glutamatergic transmission [1]
- Synaptic strength: Critical for excitatory synaptic transmission [1]
- Brain regional specificity: Highly expressed in thalamus, cortex, brainstem [1]
VGLUT2 is expressed in:
- Thalamocortical neurons
- Cerebellar granule cells
- Brainstem sensory neurons
- Subpopulations of cortical pyramidal neurons
VGLUT2 dysfunction is implicated in ALS pathogenesis [2]:
- Motor neuron vulnerability: Altered vesicular glutamate transport [3]
- Excitotoxicity: Contributes to glutamate excitotoxicity in ALS [2]
- Genetic factors: SLC17A6 variants associated with ALS risk [2]
- Therapeutic targeting: Modulating VGLUT2 function [3]
- Glutamatergic dysfunction: Altered VGLUT2 expression in AD brain [4]
- Synaptic loss: Contributes to excitatory synaptic deficits [4]
- Cognitive decline: Affects glutamatergic circuits [4]
- Thalamic dysfunction: VGLUT2 in thalamocortical projections [1]
- Excitatory deficits: Altered glutamate transmission in PD [1]
- Seizure susceptibility: VGLUT2 dysfunction affects excitatory transmission [5]
- Hyperglutamatergic state: Contributes to hyperexcitability [5]
- Glutamatergic hypothesis: VGLUT2 alterations in prefrontal cortex [1]
- Cognitive deficits: Affects thalamocortical circuits [1]
- VGLUT2 modulators: Experimental approaches to enhance function
- Gene therapy: Restoring VGLUT2 expression
- Excitotoxicity reduction: Targeting vesicular glutamate transport
- Combination therapy: With other glutamatergic modulators
- VGLUT2-Cre mice: Genetic driver line for studying glutamatergic neurons
- VGLUT2-reporter lines: Visualization of glutamatergic populations