VAChT Protein is a protein encoded by the SLC18A3 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
:: infobox .infobox-protein
VAChT (Vesicular Acetylcholine Transporter)
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; Gene
: SLC18A3
; UniProt ID
: Q9P2F6
; PDB Structures
: 7WJR, 7WJS
; Molecular Weight
: ~56 kDa (human)
; Subcellular Localization
: Synaptic vesicles of cholinergic neurons
; Protein Family
: Vesicular amine transporter (VAT) family
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VAChT (SLC18A3), also known as Vesicular Acetylcholine Transporter, is a 530-amino acid transmembrane protein that packages acetylcholine into synaptic vesicles. The protein features:
- 12 transmembrane domains: Characteristic of the vesicular transporter family
- Vesicular lumen orientation: Transports ACh into synaptic vesicles
- Proton gradient coupling: Uses V-ATPase-generated H+ gradient
- Functional homodimer: Forms functional dimers
The transporter couples the proton gradient to acetylcholine uptake against its concentration gradient.
VAChT is essential for cholinergic neurotransmission:
- ACh packaging: Packages acetylcholine into synaptic vesicles [1]
- Quantal release: Determines amount of ACh per vesicle release [1]
- Synaptic transmission: Critical for neuromuscular and central cholinergic transmission [1]
- Cholinergic identity: Co-expressed with CHAT, defines cholinergic neurons [1]
VAChT is expressed in:
- Motor neurons (neuromuscular junction)
- Basal forebrain cholinergic neurons
- Brainstem cholinergic nuclei
- Autonomic nervous system
VAChT dysfunction is implicated in AD pathogenesis [2]:
- Cholinergic degeneration: Loss of VAChT in basal forebrain [3]
- Reduced ACh release: Contributes to cognitive decline [2]
- Therapeutic targeting: VAChT as therapeutic target [3]
- Neuromuscular dysfunction: Autoantibodies affect cholinergic transmission [1]
- Synaptic vesicle depletion: VAChT function indirectly affected [1]
- Cholinergic dysfunction: VAChT in Lewy body pathology [1]
- Cognitive decline: Contributes to PD dementia [1]
- Motor neuron vulnerability: VAChT expression reduced [4]
- Neuromuscular junction: Synaptic dysfunction [4]
- Motor neuron degeneration: VAChT in affected motor neurons [1]
- Neuromuscular failure: Cholinergic transmission loss [1]
- Cholinergic enhancement: Indirect targeting of VAChT function
- Gene therapy: Experimental VAChT delivery [3]
- Symptomatic treatment: AChE inhibitors increase ACh availability
- Immunomodulation: Targeting underlying autoimmunity
- VAChT-Cre mice: Genetic access to cholinergic neurons
- VAChT-reporter lines: Visualization of cholinergic populations